Scholars@Duke
Evan Kharasch

Evan Kharasch

Merel H. Harmel Distinguished Professor of Anesthesiology
Anesthesiology, General, Vascular, High Risk Transplant & Critical Care
evan.kharasch@duke.edu
Box 3094, Anesthesiology, Durham, NC 27710
Department of Anesthesiology, Box 3094, 905 S. LaSalle, GSRB1 Room 2031, Durham, NC 27710
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Selected Publications

Intraoperative methadone administration for total mastectomy: A single center retrospective study

Journal Article Journal of Clinical Anesthesia · November 1, 2024 Background: Breast cancer is the most frequent type of cancer and the second leading cause of cancer-related mortality in women. Mastectomies remain a key component of the treatment of non-metastatic breast cancer, and strategies to treat acute postoperati ... Full text Cite

Single-dose Intraoperative Methadone for Pain Management in Pediatric Tonsillectomy: A Randomized Double-blind Clinical Trial.

Journal Article Anesthesiology · September 1, 2024 BACKGROUND: More than 500,000 elective tonsillectomies are performed in U.S. children annually. Pain after pediatric tonsillectomy is common, often severe, and undertreated. There is no consensus on the optimal management of perioperative tonsillectomy pai ... Full text Link to item Cite

Intrasubject Variability in Intravenous and Oral Probes for Hepatic and First-Pass CYP3A Activity.

Journal Article Clin Pharmacokinet · August 2024 BACKGROUND AND OBJECTIVES: Clearances and the area under the plasma concentration-time curve extrapolated to infinity (AUC0-∞) of intravenous (IV) and oral midazolam and alfentanil are probes for hepatic and first-pass cytochrome P450 3A (CYP3A) activity, ... Full text Link to item Cite

Pharmacogenetic Influence on Stereoselective Steady-State Disposition of Bupropion.

Journal Article Drug Metab Dispos · April 16, 2024 Bupropion is used for treating depression, obesity, and seasonal affective disorder, and for smoking cessation. Bupropion is commonly prescribed, but has complex pharmacokinetics and interindividual variability in metabolism and bioactivation may influence ... Full text Link to item Cite

An investigation of the potential clinical utility of critical slowing down as an early warning sign for recurrence of depression.

Journal Article J Behav Ther Exp Psychiatry · March 2024 BACKGROUND AND OBJECTIVES: Much of the burden of depressive illness is due to relapses that occur after treatment into remission. Prediction of an individual's imminent depressive relapse could lead to just-in-time interventions to prevent relapse, reducin ... Full text Link to item Cite

Natural Products Inhibition of Cytochrome P450 2B6 Activity and Methadone Metabolism.

Journal Article Drug Metab Dispos · February 14, 2024 Methadone is cleared predominately by hepatic cytochrome P450 (CYP) 2B6-catalyzed metabolism to inactive metabolites. CYP2B6 also catalyzes the metabolism of several other drugs. Methadone and CYP2B6 are susceptible to pharmacokinetic drug-drug interaction ... Full text Link to item Cite

Opioid sensitivity in treated and untreated obstructive sleep apnoea: a prospective cohort study.

Journal Article Br J Anaesth · January 2024 BACKGROUND: Opioid administration to patients with obstructive sleep apnoea (OSA) is controversial because they are believed to be more sensitive to opioids. However, objective data on opioid effects in OSA are lacking. We tested the hypothesis that subjec ... Full text Link to item Cite

Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2B6 Genotype and Methadone Therapy

Journal Article Clinical Pharmacology and Therapeutics · January 1, 2024 Methadone is a mu (μ) opioid receptor agonist used clinically in adults and children to manage opioid use disorder, neonatal abstinence syndrome, and acute and chronic pain. It is typically marketed as a racemic mixture of R- and S-enantiomers. R-methadone ... Full text Cite

Epidural methadone and morphine pharmacokinetics and clinical effects in healthy volunteers: A randomized, crossover-design trial

Journal Article British Journal of Clinical Pharmacology · January 1, 2024 Aims: Epidural opioids can provide effective analgesia for acute postoperative pain. Due to its unique physicochemical properties and long systemic elimination half-life, epidural methadone may provide lasting analgesia with minimal adverse effects; howeve ... Full text Cite

Intraoperative Methadone in Next-day Discharge Outpatient Surgery: A Randomized, Double-blinded, Dose-finding Pilot Study.

Journal Article Anesthesiology · October 1, 2023 BACKGROUND: Contemporary perioperative practice seeks to use less intraoperative opioid, diminish postoperative pain and opioid use, and enable less postdischarge opioid prescribing. For inpatient surgery, anesthesia with intraoperative methadone, compared ... Full text Link to item Cite

Morphine and Hydromorphone Effects, Side Effects, and Variability: A Crossover Study in Human Volunteers.

Journal Article Anesthesiology · July 1, 2023 BACKGROUND: Balancing between opioid analgesia and respiratory depression continues to challenge clinicians in perioperative, emergency department, and other acute care settings. Morphine and hydromorphone are postoperative analgesic standards. Nevertheles ... Full text Link to item Cite

Modeling adult COX-2 cerebrospinal fluid pharmacokinetics to inform pediatric investigation.

Journal Article Paediatr Anaesth · April 2023 AIM: Hysteresis is reported between plasma concentration and analgesic effect from nonsteroidal anti-inflammatory drugs. It is possible that the temporal delay between plasma and CSF nonsteroidal anti-inflammatory drugs mirrors this hysteresis. The tempora ... Full text Link to item Cite

Anesthesiology 2023: Ch-ch-ch-ch-changes.

Journal Article Anesthesiology · January 1, 2023 Full text Link to item Cite

Methadone pharmacogenetics in vitro and in vivo: Metabolism by CYP2B6 polymorphic variants and genetic variability in paediatric disposition.

Journal Article Br J Clin Pharmacol · November 2022 AIMS: Methadone metabolism and clearance are determined principally by polymorphic cytochrome P4502B6 (CYP2B6). Some CYP2B6 allelic variants affect methadone metabolism in vitro and disposition in vivo. We assessed methadone metabolism by CYP2B6 minor vari ... Full text Link to item Cite

Intraoperative methadone administration for total mastectomy: A single center retrospective study

Journal Article Journal of Clinical Anesthesia · November 1, 2024 Background: Breast cancer is the most frequent type of cancer and the second leading cause of cancer-related mortality in women. Mastectomies remain a key component of the treatment of non-metastatic breast cancer, and strategies to treat acute postoperati ... Full text Cite

Single-dose Intraoperative Methadone for Pain Management in Pediatric Tonsillectomy: A Randomized Double-blind Clinical Trial.

Journal Article Anesthesiology · September 1, 2024 BACKGROUND: More than 500,000 elective tonsillectomies are performed in U.S. children annually. Pain after pediatric tonsillectomy is common, often severe, and undertreated. There is no consensus on the optimal management of perioperative tonsillectomy pai ... Full text Link to item Cite

Intrasubject Variability in Intravenous and Oral Probes for Hepatic and First-Pass CYP3A Activity.

Journal Article Clin Pharmacokinet · August 2024 BACKGROUND AND OBJECTIVES: Clearances and the area under the plasma concentration-time curve extrapolated to infinity (AUC0-∞) of intravenous (IV) and oral midazolam and alfentanil are probes for hepatic and first-pass cytochrome P450 3A (CYP3A) activity, ... Full text Link to item Cite

Pharmacogenetic Influence on Stereoselective Steady-State Disposition of Bupropion.

Journal Article Drug Metab Dispos · April 16, 2024 Bupropion is used for treating depression, obesity, and seasonal affective disorder, and for smoking cessation. Bupropion is commonly prescribed, but has complex pharmacokinetics and interindividual variability in metabolism and bioactivation may influence ... Full text Link to item Cite

An investigation of the potential clinical utility of critical slowing down as an early warning sign for recurrence of depression.

Journal Article J Behav Ther Exp Psychiatry · March 2024 BACKGROUND AND OBJECTIVES: Much of the burden of depressive illness is due to relapses that occur after treatment into remission. Prediction of an individual's imminent depressive relapse could lead to just-in-time interventions to prevent relapse, reducin ... Full text Link to item Cite

Natural Products Inhibition of Cytochrome P450 2B6 Activity and Methadone Metabolism.

Journal Article Drug Metab Dispos · February 14, 2024 Methadone is cleared predominately by hepatic cytochrome P450 (CYP) 2B6-catalyzed metabolism to inactive metabolites. CYP2B6 also catalyzes the metabolism of several other drugs. Methadone and CYP2B6 are susceptible to pharmacokinetic drug-drug interaction ... Full text Link to item Cite

Opioid sensitivity in treated and untreated obstructive sleep apnoea: a prospective cohort study.

Journal Article Br J Anaesth · January 2024 BACKGROUND: Opioid administration to patients with obstructive sleep apnoea (OSA) is controversial because they are believed to be more sensitive to opioids. However, objective data on opioid effects in OSA are lacking. We tested the hypothesis that subjec ... Full text Link to item Cite

Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2B6 Genotype and Methadone Therapy

Journal Article Clinical Pharmacology and Therapeutics · January 1, 2024 Methadone is a mu (μ) opioid receptor agonist used clinically in adults and children to manage opioid use disorder, neonatal abstinence syndrome, and acute and chronic pain. It is typically marketed as a racemic mixture of R- and S-enantiomers. R-methadone ... Full text Cite

Epidural methadone and morphine pharmacokinetics and clinical effects in healthy volunteers: A randomized, crossover-design trial

Journal Article British Journal of Clinical Pharmacology · January 1, 2024 Aims: Epidural opioids can provide effective analgesia for acute postoperative pain. Due to its unique physicochemical properties and long systemic elimination half-life, epidural methadone may provide lasting analgesia with minimal adverse effects; howeve ... Full text Cite

Intraoperative Methadone in Next-day Discharge Outpatient Surgery: A Randomized, Double-blinded, Dose-finding Pilot Study.

Journal Article Anesthesiology · October 1, 2023 BACKGROUND: Contemporary perioperative practice seeks to use less intraoperative opioid, diminish postoperative pain and opioid use, and enable less postdischarge opioid prescribing. For inpatient surgery, anesthesia with intraoperative methadone, compared ... Full text Link to item Cite

Morphine and Hydromorphone Effects, Side Effects, and Variability: A Crossover Study in Human Volunteers.

Journal Article Anesthesiology · July 1, 2023 BACKGROUND: Balancing between opioid analgesia and respiratory depression continues to challenge clinicians in perioperative, emergency department, and other acute care settings. Morphine and hydromorphone are postoperative analgesic standards. Nevertheles ... Full text Link to item Cite

Modeling adult COX-2 cerebrospinal fluid pharmacokinetics to inform pediatric investigation.

Journal Article Paediatr Anaesth · April 2023 AIM: Hysteresis is reported between plasma concentration and analgesic effect from nonsteroidal anti-inflammatory drugs. It is possible that the temporal delay between plasma and CSF nonsteroidal anti-inflammatory drugs mirrors this hysteresis. The tempora ... Full text Link to item Cite

Anesthesiology 2023: Ch-ch-ch-ch-changes.

Journal Article Anesthesiology · January 1, 2023 Full text Link to item Cite

Methadone pharmacogenetics in vitro and in vivo: Metabolism by CYP2B6 polymorphic variants and genetic variability in paediatric disposition.

Journal Article Br J Clin Pharmacol · November 2022 AIMS: Methadone metabolism and clearance are determined principally by polymorphic cytochrome P4502B6 (CYP2B6). Some CYP2B6 allelic variants affect methadone metabolism in vitro and disposition in vivo. We assessed methadone metabolism by CYP2B6 minor vari ... Full text Link to item Cite

Opioids and Public Health: The Prescription Opioid Ecosystem and Need for Improved Management.

Journal Article Anesthesiology · January 1, 2022 While U.S. opioid prescribing has decreased 38% in the past decade, opioid deaths have increased 300%. This opioid paradox is poorly recognized. Current approaches to opioid management are not working, and new approaches are needed. This article reviews th ... Full text Link to item Cite

Authorship and Publication Matters: Reply.

Journal Article Anesthesiology · January 1, 2022 Full text Link to item Cite

Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6, OPRM1, and COMT Genotypes and Select Opioid Therapy.

Journal Article Clin Pharmacol Ther · October 2021 Opioids are mainly used to treat both acute and chronic pain. Several opioids are metabolized to some extent by CYP2D6 (codeine, tramadol, hydrocodone, oxycodone, and methadone). Polymorphisms in CYP2D6 have been studied for an association with the clinica ... Full text Link to item Cite

Opioid-free Anesthesia: Reply.

Journal Article Anesthesiology · October 1, 2021 Full text Link to item Cite

Anesthesiology: Reflecting and Leading.

Journal Article Anesthesiology · October 1, 2021 Full text Link to item Cite

Scientific Integrity and Misconduct-Yet Again.

Journal Article Anesthesiology · September 1, 2021 Full text Link to item Cite

Prolonged ketamine infusion modulates limbic connectivity and induces sustained remission of treatment-resistant depression.

Journal Article Psychopharmacology (Berl) · April 2021 Ketamine produces a rapid antidepressant response in over 50% of adults with treatment-resistant depression. A long infusion of ketamine may provide durable remission of depressive symptoms, but the safety, efficacy, and neurobiological correlates are unkn ... Full text Link to item Cite

Opioid-free Anesthesia: Time to Regain Our Balance.

Journal Article Anesthesiology · April 1, 2021 Full text Link to item Cite

Gold Nanorod Size-Dependent Fluorescence Enhancement for Ultrasensitive Fluoroimmunoassays.

Journal Article ACS Appl Mater Interfaces · March 10, 2021 Plasmon-enhanced fluorescence (PEF) is a simple and highly effective approach for improving the signal-to-noise ratio and sensitivity of various fluorescence-based bioanalytical techniques. Here, we show that the fluorescence enhancement efficacy of gold n ... Full text Link to item Cite

Plasma and cerebrospinal fluid pharmacokinetics of ondansetron in humans.

Journal Article Br J Clin Pharmacol · February 2021 AIMS: Changes in serotonergic sensory modulation associated with overexpression of 5-HT3 receptors in the central nervous system (CNS) have been implicated in the pathophysiology of neuropathic pain after peripheral nerve damage. 5-HT3 receptor antagonists ... Full text Link to item Cite

Uncertainty and Certainty: Reply.

Journal Article Anesthesiology · December 1, 2020 Full text Link to item Cite

Stereoselective Steady-State Disposition and Bioequivalence of Brand and Generic Bupropion in Adults.

Journal Article Clin Pharmacol Ther · November 2020 The antidepressant bupropion is stereoselectively metabolized and metabolite enantiomers have differential pharmacologic effects, but steady-state enantiomeric disposition is unknown. Controversy persists about bupropion XL 300 mg generic equivalence to br ... Full text Link to item Cite

Uncertainty and Certainty.

Journal Article Anesthesiology · July 2020 Full text Link to item Cite

Novel Coronavirus 2019 and Anesthesiology.

Journal Article Anesthesiology · June 2020 Full text Link to item Cite

Stereoselective Bupropion Hydroxylation by Cytochrome P450 CYP2B6 and Cytochrome P450 Oxidoreductase Genetic Variants.

Journal Article Drug Metab Dispos · June 2020 Bioactivation of the antidepressant and smoking cessation drug bupropion is catalyzed predominantly by CYP2B6. The metabolite hydroxybupropion derived from t-butylhydroxylation is considered to contribute to the antidepressant and smoking-cessation effects ... Full text Link to item Cite

Influence of St. John's Wort on Intravenous Fentanyl Pharmacokinetics, Pharmacodynamics, and Clinical Effects: A Randomized Clinical Trial.

Journal Article Anesthesiology · March 2020 BACKGROUND: Patients often use complementary and alternative herbal medicines, hence, potential exists for adverse herb-drug interactions. Fentanyl is metabolized by hepatic CYP3A4 and considered transported by blood-brain barrier P-glycoprotein. Both disp ... Full text Link to item Cite

Innovation in Clinical Research Regulation.

Journal Article Anesthesiology · January 2020 Full text Link to item Cite

The metabotropic glutamate receptor 5 negative allosteric modulator fenobam: pharmacokinetics, side effects, and analgesic effects in healthy human subjects.

Journal Article Pain · January 2020 Metabotropic glutamate receptor 5 (mGlu5) has been shown to modulate nociception in animals, but no mGlu5 antagonists have been developed commercially as analgesics. The mGlu5 antagonist fenobam [N-(3-chlorophenyl)-N'-(4,5-dihydro-1-methyl-4-oxo-1H-imidazo ... Full text Link to item Cite

Toward precision prescribing for methadone: Determinants of methadone deposition.

Journal Article PLoS One · 2020 BACKGROUND: Despite the World Health Organization listing methadone as an essential medication, effective dose selection is challenging, especially in racial and ethnic minority populations. Subtherapeutic doses can result in withdrawal symptoms while supr ... Full text Link to item Cite

Bioplasmonic paper-based assay for perilipin-2 non-invasively detects renal cancer.

Journal Article Kidney Int · December 2019 Renal cell carcinoma (RCC) has poor survival prognosis because it is asymptomatic at an early, more curative stage. Recently, urine perilipin-2 (PLIN-2) was demonstrated to be a sensitive and specific biomarker for the noninvasive, early detection of RCC a ... Full text Link to item Cite

Efavirenz Metabolism: Influence of Polymorphic CYP2B6 Variants and Stereochemistry.

Journal Article Drug Metab Dispos · October 2019 Efavirenz (more specifically the S-enantiomer) is a cornerstone antiretroviral therapy for treatment of HIV infection. The major primary metabolite is S-8-hydroxyefavirenz, which does not have antiretroviral activity but is neurotoxic. Cytochrome P450 2B6 ... Full text Link to item Cite

Methadone Disposition: Implementing Lessons Learned.

Journal Article J Clin Pharmacol · August 2019 Full text Link to item Cite

Observations and Observational Research.

Journal Article Anesthesiology · July 2019 Full text Link to item Cite

Opioid Sensitivity in Children with and without Obstructive Sleep Apnea.

Journal Article Anesthesiology · June 2019 BACKGROUND: Opioids are a mainstay of perioperative analgesia. Opioid use in children with obstructive sleep apnea is challenging because of assumptions for increased opioid sensitivity and assumed risk for opioid-induced respiratory depression compared to ... Full text Link to item Cite

Bioequivalence and Therapeutic Equivalence of Generic and Brand Bupropion in Adults With Major Depression: A Randomized Clinical Trial.

Journal Article Clin Pharmacol Ther · May 2019 Controversy persists about bupropion XL 300 mg generic equivalence to brand product. A prospective, randomized, double-blinded crossover in 70 adults with major depression in stable remission taking any bupropion XL 300 mg tested bioequivalence and therape ... Full text Link to item Cite

Strain-specific altered nicotine metabolism in 3,3'-diindolylmethane (DIM) exposed mice.

Journal Article Biopharm Drug Dispos · May 2019 Two indole compounds, indole-3-carbinol (I3C) and its acid condensation product, 3,3'-diindolymethane (DIM), have been shown to suppress the expression of flavin-containing monooxygenases (FMO) and to induce some hepatic cytochrome P450s (CYPs) in rats. In ... Full text Link to item Cite

Nicotine oxidation by genetic variants of CYP2B6 and in human brain microsomes.

Journal Article Pharmacol Res Perspect · April 2019 Common variation in the CYP2B6 gene, encoding the cytochrome P450 2B6 enzyme, is associated with substrate-specific altered clearance of multiple drugs. CYP2B6 is a minor contributor to hepatic nicotine metabolism, but the enzyme has been proposed as relev ... Full text Link to item Cite

Intraoperative Methadone in Same-Day Ambulatory Surgery: A Randomized, Double-Blinded, Dose-Finding Pilot Study.

Journal Article Anesth Analg · April 2019 BACKGROUND: Approximately 50 million US patients undergo ambulatory surgery annually. Postoperative opioid overprescribing is problematic, yet many patients report inadequate pain relief. In major inpatient surgery, intraoperative single-dose methadone pro ... Full text Link to item Cite

Halogen Substitution Influences Ketamine Metabolism by Cytochrome P450 2B6: In Vitro and Computational Approaches.

Journal Article Mol Pharm · February 4, 2019 Ketamine is analgesic at anesthetic and subanesthetic doses, and it has been used recently to treat depression. Biotransformation mediates ketamine effects, influencing both systemic elimination and bioactivation. CYP2B6 is the major catalyst of hepatic ke ... Full text Link to item Cite

Urinary aquaporin 1 and perilipin 2: Can these novel markers accurately characterize small renal masses and help guide patient management?

Journal Article Int J Urol · February 2019 OBJECTIVE: To evaluate the role of urine aquaporin 1 and perilipin 2 as biomarkers adjunct to renal mass biopsy in guiding the management of patients with small renal masses. METHODS: Preoperative aquaporin 1 and perilipin 2 levels in 57 patients with smal ... Full text Link to item Cite

Common Polymorphisms of CYP2B6 Influence Stereoselective Bupropion Disposition.

Journal Article Clin Pharmacol Ther · January 2019 Bupropion hydroxylation is a bioactivation and metabolic pathway, and the standard clinical CYP2B6 probe. This investigation determined the influence of CYP2B6 allelic variants on clinical concentrations and metabolism of bupropion enantiomers. Secondary o ... Full text Link to item Cite

Trusted Evidence: Discovery to Practice.

Journal Article Anesthesiology · January 2019 Full text Link to item Cite

Low-dose augmentation with buprenorphine increases emotional reactivity but not reward activity in treatment resistant mid- and late-life depression.

Journal Article Neuroimage Clin · 2019 Buprenorphine is currently being studied for treatment-resistant depression because of its rapid effect, relative safety, and unique pharmacodynamics. To understand the neural impact of buprenorphine in depression, we examined acute limbic and reward circu ... Full text Link to item Cite

Add-on plasmonic patch as a universal fluorescence enhancer

Journal Article Light: Science and Applications · December 1, 2018 Fluorescence-based techniques are the cornerstone of modern biomedical optics, with applications ranging from bioimaging at various scales (organelle to organism) to detection and quantification of a wide variety of biological species of interest. However, ... Full text Cite

Metal-Organic Framework Encapsulation Preserves the Bioactivity of Protein Therapeutics.

Journal Article Adv Healthc Mater · November 2018 Protein therapeutics are prone to lose their structure and bioactivity under various environmental stressors. This study reports a facile approach using a nanoporous material, zeolitic imidazolate framework-8 (ZIF-8), as an encapsulant for preserving the p ... Full text Link to item Cite

Stereoselective Ketamine Metabolism by Genetic Variants of Cytochrome P450 CYP2B6 and Cytochrome P450 Oxidoreductase.

Journal Article Anesthesiology · October 2018 WHAT WE ALREADY KNOW ABOUT THIS TOPIC: WHAT THIS ARTICLE TELLS US THAT IS NEW: BACKGROUND:: Human ketamine N-demethylation to norketamine in vitro at therapeutic concentrations is catalyzed predominantly by the cytochrome P4502B6 isoform (CYP2B6). The CYP2 ... Full text Link to item Cite

In Reply.

Journal Article Anesthesiology · September 2018 Full text Link to item Cite

Environmental Stability of Plasmonic Biosensors Based on Natural versus Artificial Antibody.

Journal Article Anal Chem · July 3, 2018 Plasmonic biosensors based on the refractive index sensitivity of localized surface plasmon resonance (LSPR) are considered to be highly promising for on-chip and point-of-care biodiagnostics. However, most of the current plasmonic biosensors employ natura ... Full text Link to item Cite

How central is central poststroke pain? The role of afferent input in poststroke neuropathic pain: a prospective, open-label pilot study.

Journal Article Pain · July 2018 Central poststroke pain (CPSP) is a neuropathic pain disorder, the underlying mechanisms of which are not well understood. It has been suggested that stroke-associated loss of inhibitory neurons in the spinothalamic tract causes disinhibition of thalamic n ... Full text Link to item Cite

Frontiers in Opioid Pharmacology.

Journal Article Anesthesiology · May 2018 Full text Link to item Cite

The Challenges of Translation.

Journal Article Anesthesiology · April 2018 Full text Link to item Cite

Metal-Organic Framework Encapsulation for Biospecimen Preservation

Journal Article Chemistry of Materials · February 27, 2018 Handling, transport, and storage of biospecimens such as blood and urine without refrigeration are extremely challenging. This formidable challenge leads to an inevitable reliance on a "cold chain" for shipping, handling, and storage of biospecimens throug ... Full text Cite

Ultrarobust Biochips with Metal-Organic Framework Coating for Point-of-Care Diagnosis.

Journal Article ACS Sens · February 23, 2018 Most biosensors relying on antibodies as recognition elements fail in harsh environment conditions such as elevated temperatures, organic solvents, or proteases because of antibody denaturation, and require strict storage conditions with defined shelf life ... Full text Link to item Cite

Nicotine dependence is associated with functional variation in FMO3, an enzyme that metabolizes nicotine in the brain.

Journal Article Pharmacogenomics J · January 2018 A common haplotype of the flavin-containing monooxygenase gene FMO3 is associated with aberrant mRNA splicing, a twofold reduction in in vivo nicotine N-oxidation and reduced nicotine dependence. Tobacco remains the largest cause of preventable mortality w ... Full text Link to item Cite

Rapid, Point-of-Care, Paper-Based Plasmonic Biosensor for Zika Virus Diagnosis

Journal Article Advanced Biosystems · September 1, 2017 Zika virus (ZIKV) is an increasing global health challenge. There is an urgent need for rapid, low-cost, and accurate diagnostic tests that can be broadly distributed and applied in pandemic regions. Here, an innovative, adaptable, and rapidly deployable b ... Full text Cite

Amplification of Refractometric Biosensor Response through Biomineralization of Metal–Organic Framework Nanocrystals

Journal Article Advanced Materials Technologies · July 1, 2017 Plasmonic biosensors based on the refractive index sensitivity of localized surface plasmon resonance (LSPR) are highly promising for on-chip and point-of-care diagnostics. In particular, plasmonic biosensors that rely on artificial antibodies are highly a ... Full text Cite

Clinical pharmacogenetics implementation consortium guideline (CPIC) for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants: 2016 update.

Journal Article Clin Pharmacol Ther · July 2017 CYP2D6 and CYP2C19 polymorphisms affect the exposure, efficacy and safety of tricyclic antidepressants (TCAs), with some drugs being affected by CYP2D6 only (e.g., nortriptyline and desipramine) and others by both polymorphic enzymes (e.g., amitriptyline, ... Full text Link to item Cite

Single Molecule Force Spectroscopy to Compare Natural versus Artificial Antibody-Antigen Interaction.

Journal Article Small · May 2017 Biorecognition is central to various biological processes and finds numerous applications in virtually all areas of chemistry, biology, and medicine. Artificial antibodies, produced by imprinting synthetic polymers, are designed to mimic the biological rec ... Full text Link to item Cite

Current Concepts in Methadone Metabolism and Transport.

Journal Article Clin Pharmacol Drug Dev · March 2017 Methadone is a cornerstone therapy for opioid addiction and a public health strategy for HIV/AIDS and hepatitis C reduction. Methadone is also used for acute and chronic pain. As use for chronic pain has grown, so too have adverse events. Constitutive and ... Full text Link to item Cite

Metal-Organic Framework as a Protective Coating for Biodiagnostic Chips.

Journal Article Adv Mater · February 2017 Zeolitic imidazolate framework-8 (ZIF-8) grown around antibodies anchored to plasmonic nanostructures serves as a protective layer to preserve the biorecognition ability of antibodies stored at room and elevated temperatures for several days. The biofuncti ... Full text Link to item Cite

Aromatic Functionality of Target Proteins Influences Monomer Selection for Creating Artificial Antibodies on Plasmonic Biosensors.

Journal Article ACS Appl Mater Interfaces · January 11, 2017 Natural antibodies used as biorecognition elements suffer from numerous shortcomings, such as limited chemical and environmental stability and cost. Artificial antibodies based on molecular imprinting are an attractive alternative to natural antibodies. We ... Full text Link to item Cite

Plasmonic biosensors in resource-limited settings

Conference Optics InfoBase Conference Papers · January 1, 2017 Full text Cite

Rapid, point-of-care, thermally stable paper-based plasmonic assay for Zika virus diagnosis

Conference Optics InfoBase Conference Papers · January 1, 2017 We devised innovative, adaptable, bioplasmonic paper-based devices (BPDs) that diagnose Zika infection in patient serum via optical quantification of the localized surface plasmon resonance shift due to binding of patient's anti-ZIKV-Nonstructural protein- ... Full text Cite

Role of Cytochrome P4502B6 Polymorphisms in Ketamine Metabolism and Clearance.

Journal Article Anesthesiology · December 2016 BACKGROUND: At therapeutic concentrations, cytochrome P4502B6 (CYP2B6) is the major P450 isoform catalyzing hepatic ketamine N-demethylation to norketamine in vitro. The CYP2B6 gene is highly polymorphic. The most common variant allele, CYP2B6*6, is associ ... Full text Link to item Cite

Pharmacokinetics and analgesic effects of methadone in children and adults with sickle cell disease.

Journal Article Pediatr Blood Cancer · December 2016 BACKGROUND: Vaso-occlusive episodes (VOEs) are a significant source of morbidity among children and adults with sickle cell disease (SCD). There is little information on methadone use for SCD pain. This investigation evaluated methadone pharmacokinetics in ... Full text Link to item Cite

Silk-Encapsulated Plasmonic Biochips with Enhanced Thermal Stability.

Journal Article ACS Appl Mater Interfaces · October 12, 2016 Because of their high sensitivity, cost-efficiency, and great potential as point-of-care biodiagnostic devices, plasmonic biosensors based on localized surface plasmon resonance have gained immense attention. However, most plasmonic biosensors and conventi ... Full text Link to item Cite

PEGylated Artificial Antibodies: Plasmonic Biosensors with Improved Selectivity.

Journal Article ACS Appl Mater Interfaces · September 14, 2016 Molecular imprinting, which involves the formation of artificial recognition elements or cavities with complementary shape and chemical functionality to the target species, is a powerful method to overcome a number of limitations associated with natural an ... Full text Link to item Cite

Development, validation and application of a comprehensive stereoselective LC/MS-MS assay for bupropion and oxidative, reductive, and glucuronide metabolites in human urine.

Journal Article J Chromatogr B Analyt Technol Biomed Life Sci · August 1, 2016 A stereoselective assay was developed for the quantification of bupropion and oxidative, reductive, and glucuronide metabolites (16 analytes total) in human urine. Initially, authentic glucuronide standards obtained from commercial sources were found to be ... Full text Link to item Cite

Changes: Thank You, Dr. Eisenach.

Journal Article Anesthesiology · July 2016 Full text Link to item Cite

Perioperative Opioids and Public Health.

Journal Article Anesthesiology · April 2016 Full text Link to item Cite

Development and validation of a high-throughput stereoselective LC-MS/MS assay for bupropion, hydroxybupropion, erythrohydrobupropion, and threohydrobupropion in human plasma.

Journal Article J Chromatogr B Analyt Technol Biomed Life Sci · April 1, 2016 A stereoselective analytical method was developed and validated for the quantification of bupropion, and principle metabolites hydroxybupropion, erythrohydrobupropion and threohydrobupropion in human plasma. Separation of individual enantiomers (R)-bupropi ... Full text Link to item Cite

Ninety-six hour ketamine infusion with co-administered clonidine for treatment-resistant depression: A pilot randomised controlled trial.

Journal Article World J Biol Psychiatry · April 2016 Objectives We examined the feasibility of a high-dose, 96-h infusion of ketamine in treatment-resistant depression. Methods Ten participants were randomised to receive a 96-h ketamine infusion, titrated as tolerated to a target rate of 0.6 mg/kg/h, while 1 ... Full text Link to item Cite

Fentanyl and Midazolam Are Ineffective in Reducing Episodic Intracranial Hypertension in Severe Pediatric Traumatic Brain Injury.

Journal Article Crit Care Med · April 2016 OBJECTIVE: To evaluate the clinical effectiveness of bolus-dose fentanyl and midazolam to treat episodic intracranial hypertension in children with severe traumatic brain injury. DESIGN: Retrospective cohort. SETTING: PICU in a university-affiliated childr ... Full text Link to item Cite

Developmental Pharmacology

Chapter · January 1, 2016 Full text Cite

Effect of HAART on Brain Organization and Function in HIV-Negative Subjects.

Journal Article J Neuroimmune Pharmacol · December 2015 HIV causes neural dysfunction in infected individuals. This dysfunction often manifests as cognitive symptoms and can be detected using neuroimaging. Highly active anti-retroviral therapy (HAART), in addition to providing virologic control, has reduced the ... Full text Link to item Cite

Peptide Functionalized Gold Nanorods for the Sensitive Detection of a Cardiac Biomarker Using Plasmonic Paper Devices.

Journal Article Sci Rep · November 10, 2015 The sensitivity of localized surface plasmon resonance (LSPR) of metal nanostructures to adsorbates lends itself to a powerful class of label-free biosensors. Optical properties of plasmonic nanostructures are dependent on the geometrical features and the ... Full text Link to item Cite

Methadone Pharmacogenetics: CYP2B6 Polymorphisms Determine Plasma Concentrations, Clearance, and Metabolism.

Journal Article Anesthesiology · November 2015 BACKGROUND: Interindividual variability in methadone disposition remains unexplained, and methadone accidental overdose in pain therapy is a significant public health problem. Cytochrome P4502B6 (CYP2B6) is the principle determinant of clinical methadone e ... Full text Link to item Cite

Off-Resonant Gold Superstructures as Ultrabright Minimally Invasive Surface-Enhanced Raman Scattering (SERS) Probes

Journal Article Chemistry of Materials · August 25, 2015 (Figure Presented). Surface-enhanced Raman scattering (SERS) tags that serve as exogenous contrast agents for SERS-based bioimaging are comprised of size- and shape-controlled plasmonic nanostructures. For maximum SERS activity and image contrast, the loca ... Full text Cite

Bio-Enabled Gold Superstructures with Built-In and Accessible Electromagnetic Hotspots.

Journal Article Adv Healthc Mater · July 15, 2015 The bio-enabled synthesis of a novel class of surface enhanced Raman scattering probes is presented for functional imaging with built-in and accessible electromagnetic hotspots formed between densely packed satellites grown on a plasmonic core. The superst ... Full text Link to item Cite

Differences in Methadone Metabolism by CYP2B6 Variants.

Journal Article Drug Metab Dispos · July 2015 Methadone is a long-acting opioid with considerable unexplained interindividual variability in clearance. Cytochrome P450 2B6 (CYP2B6) mediates clinical methadone clearance and metabolic inactivation via N-demethylation to 2-ethyl-1,5-dimethyl-3,3-diphenyl ... Full text Link to item Cite

The hematological effects of nitrous oxide anesthesia in pediatric patients.

Journal Article Anesth Analg · June 2015 BACKGROUND: Prolonged administration of nitrous oxide causes an increase in plasma homocysteine in children via vitamin B12 inactivation. However, it is unclear whether nitrous oxide doses used in clinical practice cause adverse hematological effects in pe ... Full text Link to item Cite

Influence of HIV antiretrovirals on methadone N-demethylation and transport.

Journal Article Biochem Pharmacol · May 15, 2015 Drug interactions involving methadone and/or HIV antiretrovirals can be problematic. Mechanisms whereby antiretrovirals induce clinical methadone clearance are poorly understood. Methadone is N-demethylated to 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolid ... Full text Link to item Cite

Evaluation of Urine Aquaporin-1 and Perilipin-2 Concentrations as Biomarkers to Screen for Renal Cell Carcinoma: A Prospective Cohort Study.

Journal Article JAMA Oncol · May 2015 IMPORTANCE: Historically, early detection of small asymptomatic kidney tumors presages better patient outcome. Screening for asymptomatic renal tumors by abdominal imaging is not cost-effective and cannot reliably distinguish benign from malignant tumors. ... Full text Link to item Cite

Steroid Anesthesia Revisited: Again.

Journal Article Anesth Analg · May 2015 Full text Link to item Cite

Urine aquaporin 1 and perilipin 2 differentiate renal carcinomas from other imaged renal masses and bladder and prostate cancer.

Journal Article Mayo Clin Proc · January 2015 OBJECTIVE: To evaluate the sensitivity and specificity of urine aquaporin 1 (AQP1) and perilipin 2 (PLIN2) concentrations to diagnose clear cell or papillary renal cell carcinoma (RCC) by comparing urine concentrations of these unique biomarkers in patient ... Full text Link to item Cite

Cyclosporine-inhibitable cerebral drug transport does not influence clinical methadone pharmacodynamics.

Journal Article Anesthesiology · December 2014 BACKGROUND: Interindividual variability and drug interaction studies suggest that blood-brain barrier drug transporters mediate human methadone brain biodistribution. In vitro and animal studies suggest that methadone is a substrate for the efflux transpor ... Full text Link to item Cite

Bioplasmonic calligraphy for multiplexed label-free biodetection.

Journal Article Biosens Bioelectron · September 15, 2014 Printable multi-marker biochips that enable simultaneous quantitative detection of multiple target biomarkers in point-of-care and resource-limited settings are a holy grail in the field of biodiagnostics. However, preserving the functionality of biomolecu ... Full text Link to item Cite

Investigating the contribution of CYP2J2 to ritonavir metabolism in vitro and in vivo.

Journal Article Biochem Pharmacol · September 1, 2014 Ritonavir, an HIV protease inhibitor, is successfully used for the prevention and treatment of HIV infections. Ritonavir pharmacokinetics are complicated by inhibition, induction and pharmacogenetics of cytochrome P450 (CYP) enzymes mediating its clearance ... Full text Link to item Cite

Automated radiochemical synthesis and biodistribution of [¹¹C]l-α-acetylmethadol ([¹¹C]LAAM).

Journal Article Appl Radiat Isot · September 2014 Long-acting opioid agonists methadone and l-α-acetylmethadol (LAAM) prevent withdrawal in opioid-dependent persons. Attempts to synthesize [(11)C]-methadone for PET evaluation of brain disposition were unsuccessful. Owing, however, to structural and pharma ... Full text Link to item Cite

Clinical Pharmacogenetics Implementation Consortium guidelines for cytochrome P450 2D6 genotype and codeine therapy: 2014 update.

Journal Article Clin Pharmacol Ther · April 2014 Codeine is bioactivated to morphine, a strong opioid agonist, by the hepatic cytochrome P450 2D6 (CYP2D6); hence, the efficacy and safety of codeine are governed by CYP2D6 activity. Polymorphisms are a major cause of CYP2D6 variability. We summarize eviden ... Full text Link to item Cite

Significance of lipid composition in a blood-brain barrier-mimetic PAMPA assay.

Journal Article J Biomol Screen · March 2014 Endothelial cells forming the blood-brain barrier limit drug access into the brain, due to tight junctions, membrane drug transporters, and unique lipid composition. Passive permeability, thought to mediate drug access, is typically tested using porcine wh ... Full text Link to item Cite

Gold nanocages with built-in artificial antibodies for label-free plasmonic biosensing

Journal Article Journal of Materials Chemistry B · January 14, 2014 We demonstrate that gold nanocages (AuNCs) with built-in artificial antibodies enable the detection of kidney injury biomarker from synthetic urine down to a concentration of 25 ng ml-1. Molecularly imprinted AuNCs exhibit excellent selectivity ... Full text Cite

Urinary concentrations of aquaporin-1 and perilipin-2 in patients with renal cell carcinoma correlate with tumor size and stage but not grade.

Journal Article Urology · January 2014 OBJECTIVE: To evaluate the trends in urine aquaporin-1 (AQP1) and perilipin 2 (PLIN2) concentrations in patients with clear cell and papillary renal cell carcinoma (RCC), we determined the relationship between the urine concentration of these biomarkers an ... Full text Link to item Cite

Cytochrome P4503A does not mediate the interaction between methadone and ritonavir-lopinavir.

Journal Article Drug Metab Dispos · December 2013 Plasma concentrations of orally administered methadone are reduced by the human immunodeficiency virus protease inhibitor combination ritonavir and lopinavir, but the mechanism is unknown. Methadone metabolism, clearance, and drug interactions have been at ... Full text Link to item Cite

High-sensitivity analysis of buprenorphine, norbuprenorphine, buprenorphine glucuronide, and norbuprenorphine glucuronide in plasma and urine by liquid chromatography-mass spectrometry.

Journal Article J Chromatogr B Analyt Technol Biomed Life Sci · November 15, 2013 A new method using ultra-fast liquid chromatography and tandem mass spectrometry (UFLC-MS/MS) was developed for the simultaneous determination of buprenorphine and the metabolites norbuprenorphine, buprenorphine-3β-glucuronide, and norbuprenorphine-3β-gluc ... Full text Link to item Cite

Cyclosporine-inhibitable blood-brain barrier drug transport influences clinical morphine pharmacodynamics.

Journal Article Anesthesiology · October 2013 BACKGROUND: The blood-brain barrier is richly populated by active influx and efflux transporters influencing brain drug concentrations. Morphine, a drug with delayed clinical onset, is a substrate for the efflux transporter P-glycoprotein in vitro and in a ... Full text Link to item Cite

A meta-analysis of CYP2D6 metabolizer phenotype and metoprolol pharmacokinetics.

Journal Article Clin Pharmacol Ther · September 2013 Metoprolol, a commonly prescribed β-blocker, is primarily metabolized by cytochrome P450 2D6 (CYP2D6), an enzyme with substantial genetic heterogeneity. Several smaller studies have shown that metoprolol pharmacokinetics is influenced by CYP2D6 genotype an ... Full text Link to item Cite

Assessing the utility of the utility function

Journal Article Anesthesiology · September 1, 2013 Full text Cite

Mechanism of autoinduction of methadone N-demethylation in human hepatocytes.

Journal Article Anesth Analg · July 2013 BACKGROUND: There is considerable interindividual and intraindividual variability in methadone metabolism and clearance. Methadone dosing is particularly challenging during initiation of therapy, because of time-dependent increases in hepatic clearance (au ... Full text Link to item Cite

Clinical Pharmacogenetics Implementation Consortium guideline for CYP2D6 and CYP2C19 genotypes and dosing of tricyclic antidepressants.

Journal Article Clin Pharmacol Ther · May 2013 Polymorphisms in CYP2D6 and CYP2C19 affect the efficacy and safety of tricyclics, with some drugs being affected by CYP2D6 only, and others by both polymorphic enzymes. Amitriptyline, clomipramine, doxepin, imipramine, and trimipramine are demethylated by ... Full text Link to item Cite

The specificity of urinary aquaporin 1 and perilipin 2 to screen for renal cell carcinoma.

Journal Article J Urol · May 2013 PURPOSE: Renal cancer is frequently asymptomatic until late stages of the disease and it has a poor prognosis when not discovered early. AQP1 and PLIN2 are recently discovered, sensitive urine biomarkers of clear cell and papillary kidney cancer. We valida ... Full text Link to item Cite

Hot spot-localized artificial antibodies for label-free plasmonic biosensing

Journal Article Advanced Functional Materials · April 12, 2013 The development of biomolecular imprinting over the last decade has raised promising perspectives in replacing natural antibodies with artificial antibodies. A significant number of reports have been dedicated to imprinting of organic and inorganic nanostr ... Full text Cite

Methadone N-demethylation by the common CYP2B6 allelic variant CYP2B6.6.

Journal Article Drug Metab Dispos · April 2013 The long-acting opioid methadone displays considerable unexplained interindividual pharmacokinetic variability. Methadone metabolism clinically occurs primarily by N-demethylation to 2-ethyl-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), catalyzed predominan ... Full text Link to item Cite

Role of cytochrome P4502B6 in methadone metabolism and clearance.

Journal Article J Clin Pharmacol · March 2013 Methadone N-demethylation in vitro is catalyzed by hepatic cytochrome P4502B6 (CYP2B6) and CYP3A4, but clinical disposition is often attributed to CYP3A4. This investigation tested the hypothesis that CYP2B6 is a prominent CYP isoform responsible for clini ... Full text Link to item Cite

Bioplasmonic paper as a platform for detection of kidney cancer biomarkers.

Journal Article Anal Chem · November 20, 2012 We demonstrate that a common laboratory filter paper uniformly adsorbed with biofunctionalized plasmonic nanostructures can serve as a highly sensitive transduction platform for rapid detection of trace bioanalytes in physiological fluids. In particular, w ... Full text Link to item Cite

P-glycoprotein is a major determinant of norbuprenorphine brain exposure and antinociception.

Journal Article J Pharmacol Exp Ther · October 2012 Norbuprenorphine is a major metabolite of buprenorphine and potent agonist of μ, δ, and κ opioid receptors. Compared with buprenorphine, norbuprenorphine causes minimal antinociception but greater respiratory depression. It is unknown whether the limited a ... Full text Link to item Cite

Estimation of the contribution of norketamine to ketamine-induced acute pain relief and neurocognitive impairment in healthy volunteers.

Journal Article Anesthesiology · August 2012 BACKGROUND: The N-methyl-D-aspartate receptor antagonist ketamine is metabolized in the liver into its active metabolite norketamine. No human data are available on the relative contribution of norketamine to ketamine-induced analgesia and side effects. On ... Full text Link to item Cite

Mechanism of efavirenz influence on methadone pharmacokinetics and pharmacodynamics.

Journal Article Clin Pharmacol Ther · April 2012 Mechanisms by which efavirenz diminishes methadone plasma concentrations are unknown. This investigation determined efavirenz influence on clinical methadone disposition and miosis, intravenous and oral alfentanil clearance (hepatic and intestinal cytochro ... Full text Link to item Cite

Getting oil and water to mix.

Journal Article Anesthesiology · March 2012 Full text Link to item Cite

Complex drug interactions of the HIV protease inhibitors 3: effect of simultaneous or staggered dosing of digoxin and ritonavir, nelfinavir, rifampin, or bupropion.

Journal Article Drug Metab Dispos · March 2012 As part of a larger clinical drug-drug interaction (DDI) study aimed at in vitro to in vivo prediction of HIV protease inhibitor metabolic and transporter-based DDIs, we measured the inductive (staggered administration) and inductive plus inhibitory (simul ... Full text Link to item Cite

Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines for codeine therapy in the context of cytochrome P450 2D6 (CYP2D6) genotype.

Journal Article Clin Pharmacol Ther · February 2012 Codeine is bioactivated to morphine, a strong opioid agonist, by the hepatic cytochrome P450 2D6 (CYP2D6); hence, the efficacy and safety of codeine as an analgesic are governed by CYP2D6 polymorphisms. Codeine has little therapeutic effect in patients who ... Full text Link to item Cite

Lack of indinavir effects on methadone disposition despite inhibition of hepatic and intestinal cytochrome P4503A (CYP3A).

Journal Article Anesthesiology · February 2012 BACKGROUND: Methadone disposition and pharmacodynamics are highly susceptible to interactions with antiretroviral drugs. Methadone clearance and drug interactions have been attributed to cytochrome P4503A4 (CYP3A4), but actual mechanisms are unknown. Drug ... Full text Link to item Cite

Pain and anesthesia

Chapter · January 1, 2012 Pain is a fundamental biological response to noxious stimuli, comprising both unpleasant physical perceptions and negative emotions. It signals actual or potential tissue damage, and elicits protective responses needed for survival, such as withdrawal (1). ... Full text Cite

In reply

Journal Article Anesthesiology · January 1, 2012 Full text Cite

Buprenorphine metabolites, buprenorphine-3-glucuronide and norbuprenorphine-3-glucuronide, are biologically active.

Journal Article Anesthesiology · December 2011 BACKGROUND: The long-lasting high-affinity opioid buprenorphine has complex pharmacology, including ceiling effects with respect to analgesia and respiratory depression. Plasma concentrations of the major buprenorphine metabolites norbuprenorphine, bupreno ... Full text Link to item Cite

Perioperative pharmacokinetics of methadone in adolescents.

Journal Article Anesthesiology · December 2011 BACKGROUND: Methadone is frequently administered to adults experiencing anesthesia and receiving pain treatment. Methadone pharmacokinetics in adults are well characterized, including the perioperative period. Methadone is also used in children. There is, ... Full text Link to item Cite

Complex drug interactions of HIV protease inhibitors 2: in vivo induction and in vitro to in vivo correlation of induction of cytochrome P450 1A2, 2B6, and 2C9 by ritonavir or nelfinavir.

Journal Article Drug Metab Dispos · December 2011 Drug-drug interactions (DDIs) with the HIV protease inhibitors (PIs) are complex, paradoxical (e.g., ritonavir/alprazolam), and involve multiple mechanisms. As part of a larger study to better understand these DDIs and to devise a framework for in vitro to ... Full text Link to item Cite

Pharmacokinetics and tissue penetration of cefoxitin in obesity: implications for risk of surgical site infection.

Journal Article Anesth Analg · October 2011 BACKGROUND: Obesity is a significant risk factor for surgical site infections (SSIs), for poorly understood reasons. SSIs are a major cause of morbidity, prolonged hospitalization, and increased health care cost. Drug disposition in general is frequently a ... Full text Link to item Cite

Nitrous oxide anesthesia and plasma homocysteine in adolescents.

Journal Article Anesth Analg · October 2011 BACKGROUND: Nitrous oxide inactivates vitamin B(12), inhibits methionine synthase, and consequently increases plasma total homocysteine (tHcy). Prolonged exposure to nitrous oxide can lead to neuropathy, spinal cord degeneration, and even death in children ... Full text Link to item Cite

Sensitivity of intravenous and oral alfentanil and pupillary miosis as minimal and noninvasive probes for hepatic and first-pass CYP3A induction.

Journal Article Clin Pharmacol Ther · July 2011 Systemic and oral clearances of alfentanil (ALF) are in vivo probes for hepatic and first-pass cytochrome P450 (CYP) 3A. Both ALF single-point plasma concentrations and miosis are surrogates for area under the concentration-time curve (AUC) and clearance a ... Full text Link to item Cite

The contribution of common CYP2A6 alleles to variation in nicotine metabolism among European-Americans.

Journal Article Pharmacogenet Genomics · July 2011 OBJECTIVE: To study the association between cytochrome P450 2A6 (CYP2A6) genotype and metabolism of nicotine to cotinine, identify functional polymorphisms, and develop a predictive genetic model of nicotine metabolism. METHODS: The conversion of deuterate ... Full text Link to item Cite

Headache outcomes following treatment of unruptured intracranial aneurysms: a prospective analysis.

Journal Article Cephalalgia · July 2011 OBJECTIVE: To analyze headache patterns prior to and following treatment of unruptured intracranial aneurysms and identify factors associated with different headache outcomes. METHODS: A prospective observational study of patients being treated for unruptu ... Full text Link to item Cite

Effect of rifampicin on S-ketamine and S-norketamine plasma concentrations in healthy volunteers after intravenous S-ketamine administration.

Journal Article Anesthesiology · June 2011 BACKGROUND: Low-dose ketamine is used as analgesic for acute and chronic pain. It is metabolized in the liver to norketamine via cytochrome P450 (CYP) enzymes. There are few human data on the involvement of CYP enzymes on the elimination of norketamine and ... Full text Link to item Cite

Complex drug interactions of HIV protease inhibitors 1: inactivation, induction, and inhibition of cytochrome P450 3A by ritonavir or nelfinavir.

Journal Article Drug Metab Dispos · June 2011 Conflicting drug-drug interaction (DDI) studies with the HIV protease inhibitors (PIs) suggest net induction or inhibition of intestinal or hepatic CYP3A. As part of a larger DDI study in healthy volunteers, we determined the effect of extended administrat ... Full text Link to item Cite

Simultaneous determination of alfentanil and midazolam in human plasma using liquid chromatography and tandem mass spectrometry.

Journal Article J Pharm Biomed Anal · June 1, 2011 A fast, sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of alfentanil and midazolam in human plasma has been developed and validated. Alfentanil and midazolam were extracted from plasma using a ... Full text Link to item Cite

Chemical and enzyme-assisted syntheses of norbuprenorphine-3-β-D-glucuronide.

Journal Article Bioconjug Chem · April 20, 2011 Norbuprenorphine-3-β-d-glucuronide (nBPN-3-β-d-G, 1) is a major phase II metabolite of buprenorphine, a pharmaceutical used for the treatment of opioid addiction. The pharmacological activity of compound 1 is not clear because investigations have been limi ... Full text Link to item Cite

Concurrent assessment of hepatic and intestinal cytochrome P450 3A activities using deuterated alfentanil.

Journal Article Clin Pharmacol Ther · April 2011 Alfentanil (ALF) is a validated probe for hepatic, first-pass, and intestinal cytochrome P450 (CYP) 3A activity, using plasma clearances, single-point concentrations, and noninvasive pupil diameter change (miosis). Assessing intravenous (i.v.) and oral dru ... Full text Link to item Cite

Automated radiosynthesis of [11C]morphine for clinical investigation.

Journal Article Appl Radiat Isot · February 2011 To meet a multiple-dose clinical evaluation of the P-gp modulation of [(11)C]morphine delivery into the human brain, radiosynthesis of [(11)C]morphine was accomplished on an automated system by N-methylation of normorphine with [(11)C]CH(3)I. A methodology ... Full text Link to item Cite

Sensitivity and specificity of urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 for the diagnosis of renal cell carcinoma.

Journal Article Am J Nephrol · 2011 BACKGROUND/AIMS: Neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule-1 (KIM-1) are urinary biomarkers of diagnostic relevance in a wide variety of acute and chronic kidney diseases. Their diagnostic sensitivity and specificity for ... Full text Link to item Cite

Urinary biomarkers for the early diagnosis of kidney cancer

Journal Article Mayo Clinic Proceedings · January 1, 2010 OBJECTIVE: To test the hypothesis that increased tumor expression of proteins such as aquaporin-1 (AQP1) and adipophilin (ADFP) in patients with renal cancer would result in increased urine AQP1 and ADFP excretion. PATIENTS AND METhODS: Prenephrectomy and ... Full text Cite

In reply

Journal Article Mayo Clinic Proceedings · January 1, 2010 Full text Cite

In response

Journal Article Anesthesia and Analgesia · January 1, 2010 Full text Cite

Blast-related brain injury: imaging for clinical and research applications: report of the 2008 st. Louis workshop.

Conference J Neurotrauma · December 2009 Blast-related traumatic brain injury (bTBI) and post-traumatic stress disorder (PTSD) have been of particular relevance to the military and civilian health care sectors since the onset of the Global War on Terror, and TBI has been called the "signature inj ... Full text Link to item Cite

Expanded studies of the pharmacokinetics and clinical effects of multidose sublingual triazolam in healthy volunteers.

Journal Article J Clin Psychopharmacol · October 2009 Previous work described the pharmacokinetics and clinical effects of multidose sublingual triazolam (Halcion; Pharmacia & Upjohn Co, Kalamazoo, Mich). This laboratory study evaluated the hypothesis that incremental dosing of triazolam produces dose-depende ... Full text Link to item Cite

The metabotropic glutamate receptor subtype 5 antagonist fenobam is analgesic and has improved in vivo selectivity compared with the prototypical antagonist 2-methyl-6-(phenylethynyl)-pyridine.

Journal Article J Pharmacol Exp Ther · September 2009 Metabotropic glutamate receptor subtype 5 (mGlu5) has been demonstrated to play a role in the modulation of numerous nociceptive modalities. When administered via peripheral, intrathecal, or systemic routes, mGlu5 antagonists have analgesic properties in a ... Full text Link to item Cite

Sevoflurane formulation water content influences degradation by Lewis acids in vaporizers.

Journal Article Anesth Analg · June 2009 BACKGROUND: Sevoflurane is produced by several manufacturers. Currently marketed sevoflurane formulations differ in their method of synthesis, impurities, containers in which they are sold, and water content. Of the various types of chemical degradation to ... Full text Link to item Cite

Methadone metabolism and clearance are induced by nelfinavir despite inhibition of cytochrome P4503A (CYP3A) activity.

Journal Article Drug Alcohol Depend · May 1, 2009 BACKGROUND: Methadone plasma concentrations are decreased by nelfinavir. Methadone clearance and the drug interactions have been attributed to CYP3A4, but actual mechanisms of methadone clearance and the nelfinavir interaction are unknown. We assessed nelf ... Full text Link to item Cite

Methadone pharmacokinetics are independent of cytochrome P4503A (CYP3A) activity and gastrointestinal drug transport: insights from methadone interactions with ritonavir/indinavir.

Journal Article Anesthesiology · March 2009 BACKGROUND: Methadone clearance is highly variable, and drug interactions are problematic. Both have been attributed to CYP3A, but actual mechanisms are unknown. Drug interactions can provide such mechanistic information. Ritonavir/indinavir, one of the ea ... Full text Link to item Cite

Mechanism of ritonavir changes in methadone pharmacokinetics and pharmacodynamics: I. Evidence against CYP3A mediation of methadone clearance.

Journal Article Clin Pharmacol Ther · October 2008 Ritonavir diminishes methadone plasma concentrations, an effect attributed to CYP3A induction, but the actual mechanisms are unknown. We determined ritonavir effects on stereoselective methadone pharmacokinetics and clinical effects (pupillary miosis) in h ... Full text Link to item Cite

Mechanism of ritonavir changes in methadone pharmacokinetics and pharmacodynamics: II. Ritonavir effects on CYP3A and P-glycoprotein activities.

Journal Article Clin Pharmacol Ther · October 2008 Ritonavir diminishes methadone plasma concentrations, an effect attributed to CYP3A induction, but the actual mechanisms are unknown. We determined short-term (2-day) and steady-state (2-week) ritonavir effects on intestinal and hepatic CYP3A4/5 (probed wi ... Full text Link to item Cite

Adverse drug reactions with halogenated anesthetics.

Journal Article Clin Pharmacol Ther · July 2008 Problems with organ toxicity from the halogenated volatile anesthetics have influenced clinical practice, anesthetic selection, and drug development for half a century.(1,2) In turn, investigations that elucidated the mechanisms of volatile anesthetics adv ... Full text Link to item Cite

Stereoselective metabolism of bupropion by cytochrome P4502B6 (CYP2B6) and human liver microsomes.

Journal Article Pharm Res · June 2008 PURPOSE: Hydroxylation of the antidepressant and smoking deterrent drug bupropion is a clinically important bioactivation and elimination pathway. Bupropion hydroxylation is catalyzed selectively by cytochrome P4502B6 (CYP2B6). CYP2B6-catalyzed bupropion h ... Full text Link to item Cite

Molecular characterization of CYP2B6 substrates.

Journal Article Curr Drug Metab · June 2008 CYP2B6 has not been as fully characterized at the molecular level as other members of the human cytochrome P450 family. As more widely used in vitro probes for characterizing the involvement of this enzyme in the metabolism of xenobiotics have become avail ... Full text Link to item Cite

Rapid clinical induction of hepatic cytochrome P4502B6 activity by ritonavir.

Journal Article Antimicrob Agents Chemother · May 2008 Ritonavir is the most potent and efficacious inhibitor of cytochrome P4503A (CYP3A), and it is used accordingly for the pharmacoenhancement of other antiretrovirals. Paradoxically, ritonavir induces the clinical metabolism and clearance of many drugs. The ... Full text Link to item Cite

Stereoselective bupropion hydroxylation as an in vivo phenotypic probe for cytochrome P4502B6 (CYP2B6) activity.

Journal Article J Clin Pharmacol · April 2008 The clearance of racemic bupropion, metabolized selectively by CYP2B6 in vitro, has been used clinically to phenotype CYP2B6 activity, polymorphisms, and drug interactions but has known limitations. Bupropion hydroxylation by CYP2B6 is stereoselective. Thi ... Full text Link to item Cite

Role of CYP2B6 in stereoselective human methadone metabolism.

Journal Article Anesthesiology · March 2008 BACKGROUND: Metabolism and clearance of racemic methadone are stereoselective and highly variable, yet the mechanism remains largely unknown. Initial in vitro studies attributed methadone metabolism to cytochrome P4503A4 (CYP3A4). CYP3A4 was also assumed r ... Full text Link to item Cite

Contribution of itraconazole metabolites to inhibition of CYP3A4 in vivo.

Journal Article Clin Pharmacol Ther · January 2008 Itraconazole (ITZ) is metabolized in vitro to three inhibitory metabolites: hydroxy-itraconazole (OH-ITZ), keto-itraconazole (keto-ITZ), and N-desalkyl-itraconazole (ND-ITZ). The goal of this study was to determine the contribution of these metabolites to ... Full text Link to item Cite

Influence of CYP3A5 genotype on the pharmacokinetics and pharmacodynamics of the cytochrome P4503A probes alfentanil and midazolam.

Journal Article Clin Pharmacol Ther · October 2007 The hepatic and first-pass cytochrome P4503A (CYP3A) probe alfentanil (ALF) is also metabolized in vitro by CYP3A5. Human hepatic microsomal ALF metabolism is higher in livers with at least one CYP3A5*1 allele and higher CYP3A5 protein content, compared wi ... Full text Link to item Cite

Stereoselective analysis of bupropion and hydroxybupropion in human plasma and urine by LC/MS/MS.

Journal Article J Chromatogr B Analyt Technol Biomed Life Sci · September 15, 2007 A sensitive, stereoselective assay using solid phase extraction and LC-MS-MS was developed and validated for the analysis of (R)- and (S)-bupropion and its major metabolite (R,R)- and (S,S)-hydroxybupropion in human plasma and urine. Plasma or glucuronidas ... Full text Link to item Cite

More than polymorphism.

Journal Article Anesth Analg · June 2007 Full text Link to item Cite

Enantiomeric metabolic interactions and stereoselective human methadone metabolism.

Journal Article J Pharmacol Exp Ther · April 2007 Methadone is administered as a racemate, although opioid activity resides in the R-enantiomer. Methadone disposition is stereoselective, with considerable unexplained variability in clearance and plasma R/S ratios. N-Demethylation of methadone in vitro is ... Full text Link to item Cite

Every breath you take, we'll be watching you.

Journal Article Anesthesiology · April 2007 Full text Link to item Cite

Pharmacokinetic interactions between buprenorphine and antiretroviral medications.

Journal Article Clin Infect Dis · December 15, 2006 Buprenorphine is used for the treatment of opioid dependence. As the number of persons receiving buprenorphine treatment and antiretroviral therapy continues to grow, so too does the existence and clinical impact of drug interactions between buprenorphine ... Full text Link to item Cite

Simultaneous measurement of in vivo P-glycoprotein and cytochrome P450 3A activities.

Journal Article J Clin Pharmacol · November 2006 Digoxin and midazolam are routinely used as probe drugs to measure in vivo activity of P-glycoprotein (P-gp) and cytochrome P450 3A4/5 (CYP3A), respectively. We investigated whether digoxin and midazolam could be coadministered to simultaneously determine ... Full text Link to item Cite

New insights into the mechanism of methoxyflurane nephrotoxicity and implications for anesthetic development (part 2): Identification of nephrotoxic metabolites.

Journal Article Anesthesiology · October 2006 BACKGROUND: Methoxyflurane nephrotoxicity results from its metabolism, which occurs by both dechlorination (to methoxydifluoroacetic acid [MDFA]) and O-demethylation (to fluoride and dichloroacetic acid [DCAA]). Inorganic fluoride can be toxic, but it rema ... Full text Link to item Cite

New insights into the mechanism of methoxyflurane nephrotoxicity and implications for anesthetic development (part 1): Identification of the nephrotoxic metabolic pathway.

Journal Article Anesthesiology · October 2006 BACKGROUND: Methoxyflurane nephrotoxicity results from biotransformation; inorganic fluoride is a toxic metabolite. Concern exists about potential renal toxicity from volatile anesthetic defluorination, but many anesthetics increase fluoride concentrations ... Full text Link to item Cite

Pharmacokinetics and pharmacodynamics of oral oxycodone in healthy human subjects: role of circulating active metabolites.

Journal Article Clin Pharmacol Ther · May 2006 BACKGROUND: In vitro experiments suggest that circulating metabolites of oxycodone are opioid receptor agonists. Clinical and animal studies to date have failed to demonstrate a significant contribution of the O-demethylated metabolite oxymorphone toward t ... Full text Link to item Cite

Gene expression profiling of nephrotoxicity from the sevoflurane degradation product fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether ("compound A") in rats.

Journal Article Toxicol Sci · April 2006 The major degradation product of the volatile anesthetic sevoflurane, the haloalkene fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (FDVE or "compound A"), is nephrotoxic in rats. FDVE undergoes complex metabolism and bioactivation, which mediate ... Full text Link to item Cite

Stereochemical aspects of itraconazole metabolism in vitro and in vivo.

Journal Article Drug Metab Dispos · April 2006 Itraconazole (ITZ) has three chiral centers and is administered clinically as a mixture of four stereoisomers. This study evaluated stereoselectivity in ITZ metabolism. In vitro experiments were carried out using heterologously expressed CYP3A4. Only (2R,4 ... Full text Link to item Cite

Pharmacokinetics and clinical effects of multidose sublingual triazolam in healthy volunteers.

Journal Article J Clin Psychopharmacol · February 2006 Triazolam is increasing in popularity as a premedication prescribed by dentists to help their fearful and anxious patients tolerate the potentially aversive nature of some dental procedures. Recent anecdotal reports suggest that incremental sublingual dosi ... Full text Link to item Cite

Single-point sampling for assessment of constitutive, induced, and inhibited cytochrome P450 3A activity with alfentanil or midazolam.

Journal Article Clin Pharmacol Ther · November 2005 INTRODUCTION: The clearances of oral and intravenous alfentanil are in vivo probes for assessing first-pass and hepatic cytochrome P450 (CYP) 3A activity. Clearance determinations require time-consuming and expensive serial blood samples and quantitative a ... Full text Link to item Cite

Sensitivity of intravenous and oral alfentanil and pupillary miosis as minimally invasive and noninvasive probes for hepatic and first-pass CYP3A activity.

Journal Article J Clin Pharmacol · October 2005 This investigation determined the ability of alfentanil miosis and single-point concentrations to detect various degrees of CYP3A inhibition. Results were compared with those for midazolam, an alternative CYP3A probe. Twelve volunteers were studied in a ra ... Full text Link to item Cite

CYP3A probes can quantitatively predict the in vivo kinetics of other CYP3A substrates and can accurately assess CYP3A induction and inhibition.

Journal Article Mol Interv · June 2005 Because the rates at which therapeutics are cleared from the body can affect their effectiveness, knowing and accounting for the variables that contribute to drug clearance is of utmost importance when designing a drug dosage regimen for patients. The acti ... Full text Link to item Cite

Pharmacogenetic determinants of human liver microsomal alfentanil metabolism and the role of cytochrome P450 3A5.

Conference Anesthesiology · March 2005 BACKGROUND: There is considerable unexplained interindividual variability in the clearance of alfentanil. Alfentanil undergoes extensive metabolism by cytochrome P4503A4 (CYP3A4). CYP3A5 is structurally similar to CYP3A4 and metabolizes most CYP3A4 substra ... Full text Link to item Cite

Metabolism of alfentanil by cytochrome p4503a (cyp3a) enzymes.

Journal Article Drug Metab Dispos · March 2005 The synthetic opioid alfentanil is an analgesic and an in vivo probe for hepatic and first-pass CYP3A activity. Alfentanil is a particularly useful CYP3A probe because pupil diameter change is a surrogate for plasma concentrations, thereby affording noninv ... Full text Link to item Cite

Central nervous system concentrations of cyclooxygenase-2 inhibitors in humans.

Journal Article Anesthesiology · February 2005 BACKGROUND: Cyclooxygenase-2 (COX-2)-selective inhibitors (coxibs) are under investigation for the potential therapy, attenuation, or prevention of neuroinflammatory and neurodegenerative disorders. Coxibs are also a significant advance in pain therapy and ... Full text Link to item Cite

Paradoxical role of cytochrome P450 3A in the bioactivation and clinical effects of levo-alpha-acetylmethadol: importance of clinical investigations to validate in vitro drug metabolism studies.

Journal Article Clin Pharmacokinet · 2005 OBJECTIVE: Levo-alpha-acetylmethadol (LAAM, levacetylmethadol) is a long-acting opioid agonist used for the prevention of opioid withdrawal. LAAM undergoes sequential N-demethylation to norLAAM and dinorLAAM, which are more potent and longer-acting than LA ... Full text Link to item Cite

Influence of sevoflurane on the metabolism and renal effects of compound a in rats

Journal Article Anesthesiology · January 1, 2005 Background: The sevoflurane degradation product compound A is nephrotoxic in rats. In contrast, patient exposure to compound A during sevoflurane anesthesia has no clinically significant renal effects. The mechanism for this difference is incompletely unde ... Full text Cite

Evaluation of first-pass cytochrome P4503A (CYP3A) and P-glycoprotein activities using alfentanil and fexofenadine in combination.

Journal Article J Clin Pharmacol · January 2005 Cytochrome P4503A (CYP3A) and P-glycoprotein (P-gp) are major determinants of oral bioavailability. Development of in vivo probe(s), for both CYP3A and P-gp, which could be administered in combination, is a current goal. Nevertheless, there is considerable ... Full text Link to item Cite

Intravenous and oral alfentanil as in vivo probes for hepatic and first-pass cytochrome P450 3A activity: noninvasive assessment by use of pupillary miosis.

Journal Article Clin Pharmacol Ther · November 2004 INTRODUCTION: Systemic clearance of intravenous (IV) alfentanil (ALF) is an in vivo probe for hepatic cytochrome P450 (CYP) 3A activity, miosis is a surrogate for plasma ALF concentrations, and IV ALF miosis is a noninvasive probe for hepatic CYP3A. This i ... Full text Link to item Cite

In vitro metabolism of cyclosporine A by human kidney CYP3A5.

Journal Article Biochem Pharmacol · November 1, 2004 The objectives of this study were to characterize and compare the metabolic profile of cyclosporine A (CsA) catalyzed by CYP3A4, CYP3A5 and human kidney and liver microsomes, and to evaluate the impact of the CYP3A5 polymorphism on product formation from p ... Full text Link to item Cite

Stereoselective determination of methadone and the primary metabolite EDDP in human plasma by automated on-line extraction and liquid chromatography mass spectrometry.

Journal Article J Chromatogr B Analyt Technol Biomed Life Sci · October 5, 2004 A sensitive stereoselective bioanalytical liquid chromatographic assay with mass spectrometric detection (LC-MS) was developed and validated for the on-line extraction and quantification of R- and S-methadone and the primary metabolite R- and S-2-ethyliden ... Full text Link to item Cite

Influence of age on the pharmacokinetics and pharmacodynamics of oral transmucosal fentanyl citrate.

Journal Article Anesthesiology · September 2004 BACKGROUND: Cancer pain is primarily a problem of older persons. Oral transmucosal fentanyl citrate (OTF) was developed to provide rapid analgesia and is the first drug specifically approved for treating breakthrough cancer pain. Fentanyl in OTF is absorbe ... Full text Link to item Cite

Role of cytochrome P4503A in cysteine S-conjugates sulfoxidation and the nephrotoxicity of the sevoflurane degradation product fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (compound A) in rats.

Journal Article Chem Res Toxicol · September 2004 The volatile anesthetic sevoflurane is degraded to fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (FDVE) in anesthesia machines. FDVE is nephrotoxic in rats. FDVE undergoes glutathione conjugation, subsequent conversion to cysteine and mercapturi ... Full text Link to item Cite

Influence of hepatic and intestinal cytochrome P4503A activity on the acute disposition and effects of oral transmucosal fentanyl citrate.

Journal Article Anesthesiology · September 2004 BACKGROUND: Oral transmucosal fentanyl citrate (OTF) was developed to provide rapid analgesia and is specifically approved for treating breakthrough cancer pain. Fentanyl in OTF is absorbed across the oral mucosa, but a considerable portion is swallowed an ... Full text Link to item Cite

Role of hepatic and intestinal cytochrome P450 3A and 2B6 in the metabolism, disposition, and miotic effects of methadone.

Journal Article Clin Pharmacol Ther · September 2004 BACKGROUND: The disposition of the long-acting opioid methadone, used to prevent opiate withdrawal and treat short- and long-lasting pain, is highly variable. Methadone undergoes N -demethylation to the primary metabolite 2-ethyl-1,5-dimethyl-3,3-diphenylp ... Full text Link to item Cite

Bioavailabilities of rectal and oral methadone in healthy subjects.

Journal Article Br J Clin Pharmacol · August 2004 AIMS: Rectal administration of methadone may be an alternative to intravenous and oral dosing in cancer pain, but the bioavailability of the rectal route is not known. The aim of this study was to compare the absolute rectal bioavailability of methadone wi ... Full text Link to item Cite

Commentary

Journal Article Aesthetic Surgery Journal · July 1, 2004 Full text Cite

The effect of quinidine, used as a probe for the involvement of P-glycoprotein, on the intestinal absorption and pharmacodynamics of methadone.

Journal Article Br J Clin Pharmacol · May 2004 AIMS: There is considerable unexplained interindividual variability in the methadone dose-effect relationship. The efflux pump P-glycoprotein (P-gp) regulates brain access and intestinal absorption of many drugs. Evidence suggests that methadone is a P-gp ... Full text Link to item Cite

Quinidine as a probe for the role of p-glycoprotein in the intestinal absorption and clinical effects of fentanyl.

Journal Article J Clin Pharmacol · March 2004 The mechanism of individual variability in the fentanyl dose-effect relationship is unknown. The efflux pump P-glycoprotein (P-gp) regulates brain access and intestinal absorption of numerous drugs. Evidence exists that fentanyl is a P-gp substrate in vitr ... Full text Link to item Cite

Sulfoxidation of cysteine and mercapturic acid conjugates of the sevoflurane degradation product fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (compound A).

Journal Article Chem Res Toxicol · March 2004 The volatile anesthetic sevoflurane is degraded in anesthesia machines to the haloalkene fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (FDVE), which can cause renal and hepatic toxicity in rats. FDVE is metabolized to S-[1,1-difluoro-2-fluoromet ... Full text Link to item Cite

Initial pharmacokinetic, safety and efficacy evaluation of nasal morphine gluconate for breakthrough pain in cancer patients.

Journal Article Pain · December 2003 Patients with controlled background pain associated with cancer frequently also experience episodes of moderate to severe intensity breakthrough pain. Opioid pharmacotherapy, particularly with oral morphine, remains the cornerstone for the management of ca ... Full text Link to item Cite

Role of P-glycoprotein in the intestinal absorption and clinical effects of morphine.

Journal Article Clin Pharmacol Ther · December 2003 INTRODUCTION: There is considerable and unexplained individual variability in the morphine dose-effect relationship. The efflux pump P-glycoprotein regulates brain access and intestinal absorption of numerous drugs. Morphine is a P-glycoprotein substrate i ... Full text Link to item Cite

Cytotoxicity of S-conjugates of the sevoflurane degradation product fluoromethyl-2,2-difluoro-1-(trifluoromethyl) vinyl ether (Compound A) in a human proximal tubular cell line.

Journal Article Toxicol Appl Pharmacol · November 15, 2003 Fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (FDVE) is a fluorinated alkene formed by degradation of the volatile anesthetic sevoflurane in anesthesia machines. FDVE is nephrotoxic in rats but not humans. Rat FDVE nephrotoxicity is attributed t ... Full text Link to item Cite

Determination of morphine and morphine glucuronides in human plasma by 96-well plate solid-phase extraction and liquid chromatography-electrospray ionization mass spectrometry.

Journal Article J Chromatogr B Analyt Technol Biomed Life Sci · October 25, 2003 There is considerable interest in quantifying morphine and its major metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G). Available assays use gas chromatography-mass spectrometry or high-performance liquid chromatography (HPLC) with ... Full text Link to item Cite

CYP2E1 activity before and after weight loss in morbidly obese subjects with nonalcoholic fatty liver disease.

Journal Article Hepatology · August 2003 Previous studies suggest that hepatic cytochrome P450 2E1 (CYP2E1) activity is increased in individuals with chronic alcoholism, nonalcoholic steatohepatitis (NASH), and morbid obesity, and may contribute to liver disease. We studied 16 morbidly obese subj ... Full text Link to item Cite

Concordance between trifluoroacetic acid and hepatic protein trifluoroacetylation after disulfiram inhibition of halothane metabolism in rats.

Journal Article Acta Anaesthesiol Scand · July 2003 BACKGROUND: Cytochrome P4502E1(CYP2E1)-mediated oxidation of halothane to a reactive intermediate (trifluoroacyl chloride) that covalently binds to hepatic proteins forming trifluoroacetylated neoantigens is believed to be the initiating event in a complex ... Full text Link to item Cite

Acute intravascular volume expansion with rapidly administered crystalloid or colloid in the setting of moderate hypovolemia.

Journal Article Anesth Analg · June 2003 UNLABELLED: Although the distribution of various crystalloid and colloid solutions at equilibrium has been well established, the acute peak expansion of intravascular volume that can be achieved with the rapid administration of crystalloid or colloid is un ... Full text Link to item Cite

Comparison of in vitro and in vivo inhibition potencies of fluvoxamine toward CYP2C19.

Conference Drug Metab Dispos · May 2003 A previous study suggested that fluvoxamine inhibition potency toward CYP1A2 is 10 times greater in vivo than in vitro. The present study was designed to determine whether the same gap exists for CYP2C19, another isozyme inhibited by fluvoxamine. In vitro ... Full text Link to item Cite

Simultaneous assessment of drug interactions with low- and high-extraction opioids: application to parecoxib effects on the pharmacokinetics and pharmacodynamics of fentanyl and alfentanil.

Journal Article Anesthesiology · April 2003 BACKGROUND: Parecoxib is a parenteral cyclooxygenase-2 (COX-2) inhibitor intended for perioperative analgesia. It is an inactive prodrug hydrolyzed in vivo to the active inhibitor valdecoxib, a substrate for hepatic cytochrome P450 3A4 (CYP3A4); hence, a p ... Full text Link to item Cite

Disposition and miotic effects of oral alfentanil: a potential noninvasive probe for first-pass cytochrome P4503A activity.

Journal Article Clin Pharmacol Ther · March 2003 BACKGROUND AND OBJECTIVES: Systemic clearance of the opioid alfentanil after intravenous administration is an excellent in vivo probe for hepatic cytochrome P4503A (CYP3A) activity and drug interactions. Alfentanil effect (miosis) is a surrogate for plasma ... Full text Link to item Cite

Gender differences in drug effects: implications for anesthesiologists.

Journal Article Acta Anaesthesiol Scand · March 2003 BACKGROUND: The gender aspect in pharmacokinetics and pharmacodynamics of anesthetics has attracted little attention. Knowledge of previous work is required to decide if gender-based differences in clinical practice is justified, and to determine the need ... Full text Link to item Cite

Disposition of nasal, intravenous, and oral methadone in healthy volunteers.

Journal Article Clin Pharmacol Ther · November 2002 OBJECTIVE: Nasal administration of many opioids demonstrates rapid uptake and fast onset of action. Nasal administration may be an alternative to intravenous and oral administration of methadone and was therefore studied in human volunteers. METHODS: The s ... Full text Link to item Cite

Low-flow sevoflurane compared with low-flow isoflurane anesthesia in patients with stable renal insufficiency.

Journal Article Anesthesiology · September 2002 BACKGROUND: Sevoflurane is degraded to compound A (CpA) by carbon dioxide absorbents containing strong base. CpA is nephrotoxic in rats. Patient exposure to CpA is increased with low fresh gas flow rates, use of Baralyme, and high sevoflurane concentration ... Full text Link to item Cite

Nasal administration of opioids for pain management in adults.

Journal Article Acta Anaesthesiol Scand · August 2002 BACKGROUND: Nasal administration of opioids may be an alternative route to intravenous, subcutaneous, oral transmucosal, oral or rectal administration in some patients. Key features may be self-administration, combined with rapid onset of action. The aim o ... Full text Link to item Cite

Biotransformation of L-cysteine S-conjugates and N-acetyl-L-cysteine S-conjugates of the sevoflurane degradation product fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (compound A) in human kidney in vitro: interindividual variability in N-acetylation, N-deacetylation, and beta-lyase-catalyzed metabolism.

Journal Article Drug Metab Dispos · February 2002 Fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (FDVE; 1) is a fluoroalkene formed by the base-catalyzed degradation of the anesthetic sevoflurane. FDVE is nephrotoxic in rats. In both rats and humans, FDVE undergoes glutathione-dependent conjugat ... Full text Link to item Cite

Comparison of Amsorb, sodalime, and Baralyme degradation of volatile anesthetics and formation of carbon monoxide and compound a in swine in vivo.

Journal Article Anesthesiology · January 2002 BACKGROUND: Consequences of volatile anesthetic degradation by carbon dioxide absorbents that contain strong base include formation of compound A from sevoflurane, formation of carbon monoxide (CO) and CO toxicity from desflurane, enflurane and isoflurane, ... Full text Link to item Cite

The influence of parecoxib: A parenteral cyclooxygenase-2 specific inhibitor, on the pharmacokinetics and clinical effects of midazolam

Journal Article Anesthesia and Analgesia · January 1, 2002 Parecoxib, a parenteral cyclooxygenase-2 inhibitor, is undergoing clinical development as an analgesic/ antiinflammatory drug for perioperative use. Parecoxib, an inactive prodrug, is hydrolyzed in vivo to valdecoxib, a substrate for hepatic cytochrome P45 ... Full text Cite

Effects of parecoxib, a parenteral COX-2-specific inhibitor, on the pharmacokinetics and pharmacodynamics of propofol

Journal Article Anesthesiology · January 1, 2002 Background: Parecoxib, a cyclooxygenase-2-specific inhibitor with intended perioperative analgesic and antiinflammatory use, is a parenterally administered inactive prodrug undergoing rapid hydrolysis in vivo to the active cyclooxygenase-2 inhibitor valdec ... Full text Cite

Transcriptional control of intestinal cytochrome P-4503A by 1alpha,25-dihydroxy vitamin D3.

Journal Article Mol Pharmacol · December 2001 It was previously shown that CYP3A4 is induced in the human intestinal Caco-2 cell model by treatment with 1alpha,25-dihydroxy vitamin D3 (1,25-D3). We demonstrate the vitamin D analog, 19-nor-1alpha,25-dihydroxy vitamin D2, is also an effective inducer of ... Full text Link to item Cite

Long-duration low-flow sevoflurane and isoflurane effects on postoperative renal and hepatic function.

Journal Article Anesth Analg · December 2001 UNLABELLED: Sevoflurane degradation by carbon dioxide absorbents during low-flow anesthesia forms the haloalkene Compound A, which causes nephrotoxicity in rats. Numerous studies have shown no effects of Compound A formation on postoperative renal function ... Full text Link to item Cite

Glutathione S-conjugation of the sevoflurane degradation product, fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (compound A) in human liver, kidney, and blood in vitro.

Journal Article Toxicol Appl Pharmacol · December 1, 2001 Fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (FDVE) is a fluorinated alkene formed by degradation of the volatile anesthetic sevoflurane in anesthesia machines. FDVE is nephrotoxic in rats and undergoes glutathione-dependent conjugation to form ... Full text Link to item Cite

In-vivo phenotyping for CYP3A by a single-point determination of midazolam plasma concentration.

Journal Article Pharmacogenetics · December 2001 We investigated whether a single plasma midazolam concentration could serve as an accurate predictor of total midazolam clearance, an established in-vivo probe measure of cytochrome P450 3A (CYP3A) activity. In a retrospective analysis of data from 224 hea ... Full text Link to item Cite

A pilot evaluation of alfentanil-induced miosis as a noninvasive probe for hepatic cytochrome P450 3A4 (CYP3A4) activity in humans.

Journal Article Clin Pharmacol Ther · December 2001 OBJECTIVE: The opioid alfentanil is a CYP3A4 substrate whose plasma clearance depends exclusively on hepatic CYP3A4 activity. Alfentanil clearance is an excellent in vivo probe for hepatic CYP3A4 activity and drug interactions in humans. However, such phar ... Full text Link to item Cite

Fluvoxamine-theophylline interaction: gap between in vitro and in vivo inhibition constants toward cytochrome P4501A2.

Journal Article Clin Pharmacol Ther · November 2001 OBJECTIVE: Several reports indicate that fluvoxamine decreases the clearance of cytochrome P4501A2 (CYP1A2) substrates. This study compared in vitro and in vivo inhibition potencies of fluvoxamine toward CYP1A2 with an approach based on inhibition constant ... Full text Link to item Cite

Evaluation of fluoride release from commercially available fluoride varnishes.

Journal Article J Am Dent Assoc · October 2001 BACKGROUND: The authors conducted a study to evaluate the fluoride released from two fluoride varnishes: Duraphat (Colgate-Palmolive Co., New York) and Duraflor (Pharmascience Inc., Montreal). Fluoride-release information for these commercially available d ... Full text Link to item Cite

Metabolism of methadone and levo-alpha-acetylmethadol (LAAM) by human intestinal cytochrome P450 3A4 (CYP3A4): potential contribution of intestinal metabolism to presystemic clearance and bioactivation.

Journal Article J Pharmacol Exp Ther · September 2001 Methadone and levo-alpha-acetylmethadol (LAAM) are opioid agonists used for analgesia and preventing opiate withdrawal. Methadone is sequentially N-demethylated to the inactive metabolites 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethy ... Link to item Cite

Pharmacokinetics and clinical effects of sublingual triazolam in pediatric dental patients.

Journal Article J Clin Psychopharmacol · June 2001 The purpose of this investigation was to describe the pharmacokinetics of sublingual triazolam in children. Nine healthy children (64-98 months old) received 0.25 or 0.375 mg of sublingual triazolam before dental treatment. Plasma triazolam concentrations ... Full text Link to item Cite

Metabolism of levo-alpha-Acetylmethadol (LAAM) by human liver cytochrome P450: involvement of CYP3A4 characterized by atypical kinetics with two binding sites.

Journal Article J Pharmacol Exp Ther · April 2001 levo-alpha-Acetylmethadol (LAAM) is a long-acting opioid agonist prodrug used for preventing opiate withdrawal. LAAM undergoes bioactivation via sequential N-demethylation to nor-LAAM and dinor-LAAM, which are more potent and longer-acting than LAAM. This ... Link to item Cite

Speed of recovery and side-effect profile of sevoflurane sedation compared with midazolam.

Journal Article Anesthesiology · January 2001 BACKGROUND: Sedation for surgical procedures performed with regional or local anesthesia has usually been achieved with intravenous medications, whereas the use of volatile anesthetics has been limited. The use of sevoflurane for sedation has been suggeste ... Full text Link to item Cite

Bispectral index monitoring during sedation with sevoflurane, midazolam, and propofol

Journal Article Anesthesiology · January 1, 2001 Background: Bispectral Index (BIS) has been used to measure sedation depth. Ideally, to guide anesthetic management, range of BIS scores at different sedation levels should not overlap, and BIS should be independent of drug used. This study assessed abilit ... Full text Cite

Halothane-dependent lipid peroxidation in human liver microsomes is catalyzed by cytochrome P4502A6 (CYP2A6)

Journal Article Anesthesiology · January 1, 2001 Halothane is extensively (approximately 50%) metabolized in humans and undergoes both oxidative and reductive cytochrome P450-catalyzed hepatic biotransformation. Halothane is reduced under low oxygen tensions by CYP2A6 and CYP3A4 in human liver microsome ... Full text Cite

Contribution of CYP2E1 and CYP3A to acetaminophen reactive metabolite formation.

Journal Article Clin Pharmacol Ther · March 2000 BACKGROUND: CYP2E1, 1A2, and 3A4 have all been implicated in the formation of N-acetyl-p-benzoquinone imine (NAPQI), the reactive intermediate of acetaminophen (INN, paracetamol), in studies in human liver microsomes and complementary deoxyribonucleic acid ... Full text Link to item Cite

Endotracheal lidocaine administration via an esophageal combitube.

Journal Article J Emerg Med · February 2000 The purpose of this study was to test the hypothesis that lidocaine is systemically absorbed after administration via a Combitube placed in the esophagus, and that therapeutically significant plasma lidocaine concentrations can be attained using this route ... Full text Link to item Cite

Human halothane metabolism, lipid peroxidation, and cytochromes P(450)2A6 and P(450)3A4.

Journal Article Eur J Clin Pharmacol · 2000 OBJECTIVE: Halothane undergoes both oxidative and reductive metabolism by cytochrome P450 (CYP), respectively causing rare immune-mediated hepatic necrosis and common, mild subclinical hepatic toxicity. Halothane also causes lipid peroxidation in rodents i ... Full text Link to item Cite

Single-dose methoxsalen effects on human cytochrome P-450 2A6 activity.

Journal Article Drug Metab Dispos · January 2000 Methoxsalen (8-methoxypsoralen) is an effective and selective mechanism-based inhibitor of human hepatic cytochrome P-450 (CYP)2A6 in vitro, and may have utility as a clinical probe for CYP2A6-catalyzed xenobiotic metabolism in humans in vivo. This investi ... Link to item Cite

Putting the brakes on anesthetic breakdown.

Journal Article Anesthesiology · November 1999 Full text Link to item Cite

Compound A uptake and metabolism to mercapturic acids and 3,3,3-trifluoro-2-fluoromethoxypropanoic acid during low-flow sevoflurane anesthesia: biomarkers for exposure, risk assessment, and interspecies comparison.

Journal Article Anesthesiology · November 1999 BACKGROUND: Sevoflurane is degraded during low-flow anesthesia to fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether ("compound A"), which causes renal necrosis in rats but is not known to cause nephrotoxicity in surgical patients. Compound A is meta ... Full text Link to item Cite

Acute renal failure after cardiopulmonary bypass in related to decreased serum ferritin levels.

Journal Article J Am Soc Nephrol · November 1999 Acute renal failure (ARF) requiring dialysis occurs in up to 4% of patients after cardiopulmonary bypass (CPB). CPB leads to the generation of intravascular free hemoglobin, resulting in increased endothelial and renal tubular cell free iron, which is asso ... Full text Link to item Cite

Dose-dependent metabolism of fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (compound A), an anesthetic degradation product, to mercapturic acids and 3,3,3-trifluoro-2-(fluoromethoxy)propanoic acid in rats.

Journal Article Toxicol Appl Pharmacol · October 1, 1999 The volatile anesthetic sevoflurane is degraded in anesthesia machines to fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (FDVE), to which humans are exposed. FDVE is metabolized in rats and humans to two alkane and two alkene glutathione S-conjug ... Full text Link to item Cite

Duration of cytochrome P-450 2E1 (CYP2E1) inhibition and estimation of functional CYP2E1 enzyme half-life after single-dose disulfiram administration in humans.

Journal Article J Pharmacol Exp Ther · October 1999 Disulfiram (DSF) is a mechanism-based inhibitor of cytochrome P-450 2E1 (CYP2E1), resulting in loss of CYP2E1 protein and activity, which may be useful in preventing CYP2E1-mediated xenobiotic toxicity. The duration of inhibition after a single DSF dose is ... Link to item Cite

Intraindividual variability in male hepatic CYP3A4 activity assessed by alfentanil and midazolam clearance.

Journal Article J Clin Pharmacol · July 1999 Clinical investigations using isoform-selective probes to phenotype cytochrome P450 activity and interaction studies using isoform-selective inhibitors to determine P450 involvement in drug metabolism assume minimal interday variability in P450 activity. C ... Full text Link to item Cite

Lack of single-dose disulfiram effects on cytochrome P-450 2C9, 2C19, 2D6, and 3A4 activities: evidence for specificity toward P-450 2E1.

Journal Article Drug Metab Dispos · June 1999 Disulfiram and its primary metabolite diethyldithiocarbamate are effective mechanism-based inhibitors of cytochrome P-450 2E1 (CYP2E1)1 in vitro. Single-dose disulfiram diminishes CYP2E1 activity in vivo and has been used to identify CYP2E1 participation i ... Link to item Cite

Comparison of renal function following anesthesia with low-flow sevoflurane and isoflurane.

Journal Article J Clin Anesth · May 1999 STUDY OBJECTIVE: To evaluate postoperative renal function after patients were administered sevoflurane under conditions designed to generate high concentrations of compound A. STUDY DESIGN AND SETTING: A multicenter (11 sites), multinational, open-label, r ... Full text Link to item Cite

Menstrual cycle variability in midazolam pharmacokinetics.

Journal Article J Clin Pharmacol · March 1999 Activity of cytochrome P450 3A4 (CYP3A4), the most abundant human P450 isoform and responsible for metabolizing approximately half of all therapeutic agents, has been speculated to vary during the menstrual cycle. This investigation evaluated CYP3A4 activi ... Link to item Cite

Clinical isoflurane metabolism by cytochrome P450 2E1.

Journal Article Anesthesiology · March 1999 BACKGROUND: Some evidence suggests that isoflurane metabolism to trifluoroacetic acid and inorganic fluoride by human liver microsomes in vitro is catalyzed by cytochrome P450 2E1 (CYP2E1). This investigation tested the hypothesis that P450 2E1 predominant ... Full text Link to item Cite

Mechanism of disulfiram inhibition of P450 2E1 in human liver microsomes

Conference Journal of Investigative Medicine · January 1, 1999 Numerous environmental contaminants and some therapeutic drugs can cause hepatotoxicity when metabolized by cytochrome P450 2E1. Disulfiram and its primary metabolite diethydithiocarbamate (DDTC) inhibit P450 2E1 in vitro and in vivo, and disulfiram may pr ... Cite

[Compound A: toxicology and clinical relevance].

Journal Article Anaesthesist · November 1998 Sevoflurane, like all currently used volatile anaesthetics, is degraded by carbon dioxide absorbents. The most significant degradant is a haloalkene known trivially as "compound A". Compound A is nephrotoxic in rats and, at higher doses, in nonhuman primat ... Full text Link to item Cite

Does ketamine-mediated N-methyl-D-aspartate receptor antagonism cause schizophrenia-like oculomotor abnormalities?

Journal Article Neuropsychopharmacology · November 1998 Evidence from histological and pharmacological challenge studies indicates that N-methyl-D-aspartate (NMDA) receptor hypofunction may play an important role in the pathophysiology of schizophrenia. Our goal was to characterize effects of NMDA hypofunction ... Full text Link to item Cite

Mechanistic aspects of carbon monoxide formation from volatile anesthetics.

Journal Article Anesthesiology · October 1998 BACKGROUND: Desflurane, enflurane and isoflurane can be degraded to carbon monoxide (CO) by carbon dioxide absorbents, whereas sevoflurane and halothane form negligible amounts of CO. Carbon monoxide formation is greater with drier absorbent, and with bari ... Full text Link to item Cite

Single-dose disulfiram does not inhibit CYP2A6 activity.

Journal Article Clin Pharmacol Ther · July 1998 BACKGROUND: Disulfiram and its primary metabolite diethyldithiocarbamate are effective mechanism-based inhibitors of human liver cytochrome P450 2E1 (CYP2E1) in vitro. A single dose of disulfiram, which significantly diminishes human P450 2E1 activity in v ... Full text Link to item Cite

Endotracheal administration of flumazenil.

Journal Article Am J Emerg Med · July 1998 Full text Link to item Cite

Role of the renal cysteine conjugate beta-lyase pathway in inhaled compound A nephrotoxicity in rats.

Journal Article Anesthesiology · June 1998 BACKGROUND: The sevoflurane degradation product compound A is nephrotoxic in rats and undergoes metabolism to glutathione and cysteine S-conjugates, with further metabolism by renal cysteine conjugate beta-lyase to reactive intermediates. Evidence suggests ... Full text Link to item Cite

Endotracheal flumazenil: a new route of administration for benzodiazepine antagonism.

Journal Article Am J Emerg Med · March 1998 The purpose of this study was to determine if flumazenil is absorbed from broncho-pulmonary tissue after intratracheal administration and whether therapeutically significant plasma concentrations can be obtained. Six elective surgical patients received a d ... Full text Link to item Cite

Absence of biochemical evidence for renal and hepatic dysfunction after 8 hours of 1.25 minimum alveolar concentration sevoflurane anesthesia in volunteers.

Journal Article Anesthesiology · March 1998 BACKGROUND: Sevoflurane is degraded by carbon dioxide absorbents to a difluorovinyl ether (compound A) that can cause renal and hepatic injury in rats. The present study applied sensitive markers of renal and hepatic function to determine the safety of pro ... Full text Link to item Cite

Anesthetic effects on the glycerol model of rhabdomyolysis-induced acute renal failure in rats.

Journal Article J Am Soc Nephrol · February 1998 Isoflurane, the most widely used inhalational anesthetic, releases inorganic fluoride during its metabolism by the cytochrome P450 system. Recent experimental data indicate that when cultured proximal tubular cells are exposed to inorganic fluoride, they b ... Full text Link to item Cite

Acute tolerance and reversal of the motor control effects of midazolam.

Journal Article Pharmacol Biochem Behav · February 1998 The purpose of this study was to determine whether acute tolerance develops to the motor control effects of the short-acting benzodiazepine, midazolam. Using a bolus and constant infusion scheme, 40 healthy adults received a 70-min intravenous infusion of ... Full text Link to item Cite

Psychedelic effects of ketamine in healthy volunteers: relationship to steady-state plasma concentrations.

Journal Article Anesthesiology · January 1998 BACKGROUND: Ketamine has been associated with a unique spectrum of subjective "psychedelic" effects in patients emerging from anesthesia. This study quantified these effects of ketamine and related them to steady-state plasma concentrations. METHODS: Ketam ... Full text Link to item Cite

Optimal rehydration of desiccated CO2 absorbents.

Journal Article Anesthesiology · December 1997 Full text Link to item Cite

Myocardial ischemia and adverse cardiac outcomes in cardiac patients undergoing noncardiac surgery with sevoflurane and isoflurane. Sevoflurane Ischemia Study Group.

Journal Article Anesth Analg · November 1997 UNLABELLED: Sevoflurane is associated with less tachycardia and coronary vasodilation than isoflurane and thus might be associated with less myocardial ischemia. This multicenter study examined the incidence of myocardial ischemia and adverse cardiac outco ... Full text Link to item Cite

Cost-effective reduction of neuromuscular-blocking drug expenditures.

Journal Article Anesthesiology · November 1997 BACKGROUND: Anesthetic drug expenditures have been a focus of cost-containment efforts. The aim of this study was to determine whether expenditures for neuromuscular-blocking agents could be reduced without compromising outcome, and to determine whether su ... Full text Link to item Cite

Fentanyl metabolism by human hepatic and intestinal cytochrome P450 3A4: implications for interindividual variability in disposition, efficacy, and drug interactions.

Journal Article Drug Metab Dispos · September 1997 The synthetic opioid fentanyl undergoes extensive metabolism in humans. Systemic elimination occurs primarily by hepatic metabolism. When administered as a lozenge for oral transmucosal absorption, swallowed fentanyl is subject to first pass metabolism in ... Link to item Cite

Keep the blood red...the right way.

Journal Article Anesthesiology · August 1997 Full text Link to item Cite

Transition to post-operative epidural or patient-controlled intravenous analgesia following total intravenous anaesthesia with remifentanil and propofol for abdominal surgery.

Journal Article Eur J Anaesthesiol · July 1997 Remifentanil is an ultrashort acting mu opioid, well suited to total intravenous (i.v.) anaesthesia. Pain immediately following emergence from anaesthesia is a potential problem because of the rapid offset. This study investigated the transition from remif ... Full text Link to item Cite

The role of cytochrome P450 3A4 in alfentanil clearance. Implications for interindividual variability in disposition and perioperative drug interactions.

Journal Article Anesthesiology · July 1997 BACKGROUND: There is considerable unexplained variability in alfentanil pharmacokinetics, particularly systemic clearance. Alfentanil is extensively metabolized in vivo, and thus systemic clearance depends on hepatic biotransformation. Cytochrome P450 3A4 ... Full text Link to item Cite

Assessment of cytochrome P450 3A4 activity during the menstrual cycle using alfentanil as a noninvasive probe.

Journal Article Anesthesiology · July 1997 BACKGROUND: Gender-dependent differences in cytochrome P450 activity, drug metabolism, drug elimination, and their clinical consequences are increasingly apparent. P450 3A4 is the most abundant P450 isoform in the human liver and is responsible for metabol ... Full text Link to item Cite

Assessment of low-flow sevoflurane and isoflurane effects on renal function using sensitive markers of tubular toxicity.

Journal Article Anesthesiology · June 1997 BACKGROUND: Carbon dioxide absorbents degrade sevoflurane, particularly at low gas flow rates, to fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (compound A). Compound A causes renal proximal tubular injury in rats but has had no effect on blood ... Full text Link to item Cite

Spectrum and subcellular determinants of fluorinated anesthetic-mediated proximal tubular injury.

Journal Article Am J Pathol · June 1997 Currently used fluorinated anesthetics are chemically related to methoxyflurane (MF), a drug that caused many cases of clinical acute renal failure during previous widespread use. To determine whether newer fluorinated anesthetics might also have nephrotox ... Link to item Cite

Pharmacokinetics of oral triazolam in children.

Journal Article J Clin Psychopharmacol · June 1997 The purpose of this study was to determine the pharmacokinetic behavior of triazolam in children. Nine healthy children, aged 6 to 9 years, received oral triazolam (0.025 mg/kg suspended in Kool-Aid, Kraft General Foods, Chicago, IL) before dental treatmen ... Full text Link to item Cite

Determination of the halothane metabolites trifluoroacetic acid and bromide in plasma and urine by ion chromatography.

Journal Article J Chromatogr B Biomed Sci Appl · May 9, 1997 Halothane (CF3CHClBr), a widely used volatile anesthetic, undergoes extensive biotransformation in humans. Oxidative halothane metabolism yields the stable metabolites trifluoroacetic acid and bromide which can be detected in plasma and urine. To date, ana ... Full text Link to item Cite

Cytochrome P450 2E1 is the principal catalyst of human oxidative halothane metabolism in vitro.

Journal Article J Pharmacol Exp Ther · April 1997 The volatile anesthetic halothane undergoes substantial biotransformation generating metabolites that mediate hepatotoxicity. Aerobically, halothane undergoes cytochrome P450-catalyzed oxidation to trifluoroacetic acid (TFA), bromide and a reactive interme ... Link to item Cite

Cytochrome P450 and volatile anesthetic metabolism: From benchtop to bedside

Journal Article Anesthesia and Resuscitation · January 1, 1997 The toxicity of volatile anesthetics is intimately related to their metabolism by cytochrome P450. The fluorinated ether anesthetics, such as methoxyflurane, undergo P450-catalyzed metabolism which liberates inorganic fluoride ion. Excessive fluoride produ ... Cite

Pharmacovigilance and safety aspects of sevoflurane.

Journal Article Acta Anaesthesiol Scand Suppl · 1997 Link to item Cite

Role of renal cysteine conjugate beta-lyase in the mechanism of compound A nephrotoxicity in rats.

Journal Article Anesthesiology · January 1997 BACKGROUND: The sevoflurane degradation product compound A is nephrotoxic in rats, in which it undergoes extensive metabolism to glutathione and cysteine S-conjugates. The mechanism of compound A nephrotoxicity in rats is unknown. Compound A nephrotoxicity ... Full text Link to item Cite

Rehydration of desiccated baralyme prevents carbon monoxide formation from desflurane in an anesthesia machine

Journal Article Anesthesiology · January 1, 1997 Background: Desiccated carbon dioxide absorbents degrade desflurane, enflurane, and isoflurane to carbon monoxide (CO) in vitro and in anesthesia machines, which can result in significant clinical CO exposure. Carbon monoxide formation is highest from desf ... Full text Cite

Psychotomimetic effects of subanesthetic doses of ketamine: Dose versus effect relationships

Journal Article Proceedings of the Western Pharmacology Society · December 1, 1996 Psychotomimetic emergence phenomena following general anesthesia with ketamine are well documented, and affect 5-30% of patients. The psychotomimetic effects of subanesthetic doses of ketamine have been less well studied. We administered ketamine or saline ... Cite

Renal metabolism and factors affecting the degradation of sevoflurane

Journal Article Acta Anaesthesiologica Scandinavica, Supplement · December 1, 1996 Cite

Human reductive halothane metabolism in vitro is catalyzed by cytochrome P450 2A6 and 3A4.

Journal Article Drug Metab Dispos · September 1996 The anesthetic halothane undergoes extensive oxidative and reductive biotransformation, resulting in metabolites that cause hepatotoxicity. Halothane is reduced anaerobically by cytochrome P450 (P450) to the volatile metabolites 2-chloro-1,1-difluoroethene ... Link to item Cite

Evidence for metabolism of fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether (compound A), a sevoflurane degradation product, by cysteine conjugate beta-lyase.

Journal Article Chem Res Toxicol · June 1996 The volatile anesthetic sevoflurane is degraded to fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether (FDVE), a potent rat nephrotoxin. In rats in vivo, FDVE undergoes glutathione conjugation and metabolism to cysteine conjugates, whose bioactivation ... Full text Link to item Cite

P450-dependent and nonenzymatic human liver microsomal defluorination of fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (compound A), a sevoflurane degradation product.

Journal Article Drug Metab Dispos · June 1996 The volatile anesthetic sevoflurane is degraded by strong bases in the carbon dioxide absorbent in clinical anesthesia machines to fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether (FDVE, also called "Compound A"). FDVE is nephrotoxic in rats, where ... Link to item Cite

The hemodynamic and renal effects of sevoflurane and isoflurane in patients with coronary artery disease and chronic hypertension. Sevoflurane Ischemia Study Group.

Journal Article Anesth Analg · June 1996 In patients without significant cardiovascular disease, the hemodynamic effects of sevoflurane and isoflurane are similar; however, the hemodynamic effects of sevoflurane in patients with hypertension and ischemic heart disease are unknown. To examine the ... Full text Link to item Cite

Identification of the enzyme responsible for oxidative halothane metabolism: implications for prevention of halothane hepatitis.

Journal Article Lancet · May 18, 1996 BACKGROUND: Fulminant hepatic necrosis ("halothane hepatitis") is an unusual and often fatal complication of halothane anaesthesia. It is mediated by immune sensitisation in susceptible individuals to trifluoroacetylated liver protein neoantigens, formed b ... Full text Link to item Cite

Inhibition of sulfamethoxazole hydroxylamine formation by fluconazole in human liver microsomes and healthy volunteers.

Journal Article Clin Pharmacol Ther · March 1996 Sulfamethoxazole toxicity is putatively initiated by the formation of a hydroxylamine metabolite by cytochromes P450. If this reaction could be inhibited, toxicity may decrease. We have studied--in vitro and in vivo--fluconazole, ketoconazole, and cimetidi ... Full text Link to item Cite

Identification in rat bile of glutathione conjugates of fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether, a nephrotoxic degradate of the anesthetic agent sevoflurane.

Journal Article Chem Res Toxicol · March 1996 Recent studies have indicated that the nephrotoxicity of fluoromethyl 2,2-difluoro-1-(trifluoromethyl)vinyl ether ("Compound A"), a breakdown product of the inhaled anesthetic sevoflurane, may be mediated by a reactive intermediate(s) generated via the cys ... Full text Link to item Cite

Metabolism and toxicity of the new anesthetic agents.

Conference Acta Anaesthesiol Belg · 1996 Human biotransformation of the newer anesthetics, desflurane and sevoflurane, has been characterized in vitro and in vivo. Major metabolites of desflurane are inorganic fluoride and trifluoroacyl chloride, which may bind to tissue proteins or form trifluor ... Link to item Cite

Biotransformation of sevoflurane.

Journal Article Anesth Analg · December 1995 Several characteristics of sevoflurane biotransformation are apparent from the preceding investigations. Metabolism is rapid, with fluoride and HFIP appearing in plasma within minutes after the start of sevoflurane administration (38-40,51). Peak plasma fl ... Full text Link to item Cite

Stereoselective metabolism of enflurane by human liver cytochrome P450 2E1.

Journal Article Drug Metab Dispos · December 1995 The toxicity of the chiral fluorinated volatile anesthetics halothane, enflurane, and isoflurane is closely related to their metabolism by hepatic cytochrome P450. Although individual anesthetic enantiomers have been shown to exhibit a difference in anesth ... Link to item Cite

Designing safer chemicals: predicting the rates of metabolism of halogenated alkanes.

Journal Article Proc Natl Acad Sci U S A · November 21, 1995 A computational model is presented that can be used as a tool in the design of safer chemicals. This model predicts the rate of hydrogen-atom abstraction by cytochrome P450 enzymes. Excellent correlations between biotransformation rates and the calculated ... Full text Link to item Cite

Metabolism of dapsone to its hydroxylamine by CYP2E1 in vitro and in vivo.

Journal Article Clin Pharmacol Ther · November 1995 Dapsone toxicity is putatively initiated by formation of a hydroxylamine metabolite by cytochromes P450. In human liver microsomes, the kinetics of P450-catalyzed N-oxidation of dapsone were biphasic, with the Michaelis-Menten constants of 0.14 +/- 0.05 an ... Full text Link to item Cite

Sevoflurane, fluoride ion, and renal toxicity.

Journal Article Anesthesiology · July 1995 Full text Link to item Cite

Clinical sevoflurane metabolism and disposition. II. The role of cytochrome P450 2E1 in fluoride and hexafluoroisopropanol formation.

Journal Article Anesthesiology · June 1995 BACKGROUND: Sevoflurane is metabolized to free fluoride and hexafluoroisopropanol (HFIP). Cytochrome P450 2E1 is the major isoform responsible for sevoflurane metabolism by human liver microsomes in vitro. This investigation tested the hypothesis that P450 ... Full text Link to item Cite

Clinical sevoflurane metabolism and disposition. I. Sevoflurane and metabolite pharmacokinetics.

Journal Article Anesthesiology · June 1995 BACKGROUND: Sevoflurane has low blood and tissue solubility and is metabolized to free fluoride and hexafluoroisopropanol (HFIP). Although sevoflurane uptake and distribution and fluoride formation have been described, the pharmacokinetics of HFIP formatio ... Full text Link to item Cite

Nephrotoxicity of sevoflurane compound A [fluoromethyl-2,2-difluoro-1-(trifluoromethyl)vinyl ether] in rats: evidence for glutathione and cysteine conjugate formation and the role of renal cysteine conjugate beta-lyase.

Journal Article Biochem Biophys Res Commun · May 16, 1995 Compound A, which is a breakdown product of the volatile anesthetic sevoflurane, is nephrotoxic in rats, although the mechanism of this toxicity is unknown. In the present investigation, the role of glutathione conjugation, glutathione conjugate processing ... Full text Link to item Cite

Catalytic role of cytochrome P4503A4 in multiple pathways of alfentanil metabolism.

Journal Article Drug Metab Dispos · April 1995 The synthetic opioid alfentanil (ALF) undergoes extensive metabolism via two major pathways: piperidine nitrogen dealkylation to noralfentanil (NA) and amide nitrogen dealkylation to N-phenylpropionamide (AMX). It is unknown whether AMX results from amide ... Link to item Cite

Human kidney methoxyflurane and sevoflurane metabolism. Intrarenal fluoride production as a possible mechanism of methoxyflurane nephrotoxicity.

Journal Article Anesthesiology · March 1995 BACKGROUND: Methoxyflurane nephrotoxicity is mediated by cytochrome P450-catalyzed metabolism to toxic metabolites. It is historically accepted that one of the metabolites, fluoride, is the nephrotoxin, and that methoxyflurane nephrotoxicity is caused by p ... Full text Link to item Cite

Gas chromatographic-mass spectrometric analysis of alfentanil metabolites. Application to human liver microsomal alfentanil biotransformation.

Journal Article J Chromatogr B Biomed Appl · October 3, 1994 The short-acting synthetic opioid alfentanil undergoes extensive biotransformation to several metabolites. A gas chromatographic-mass spectrometric assay, using selected-ion monitoring and deuterated internal standards, was developed for quantitating the p ... Full text Link to item Cite

Determination of alfentanil and noralfentanil in human plasma by gas chromatography-mass spectrometry.

Journal Article J Chromatogr B Biomed Appl · August 5, 1994 This report describes a simple gas chromatographic-mass spectrometric (GC-MS) assay for the simultaneous analysis of alfentanil and its major metabolite, noralfentanil, in human plasma. The method facilitates the processing of numerous samples for pharmaco ... Full text Link to item Cite

Clinical enflurane metabolism by cytochrome P450 2E1.

Journal Article Clin Pharmacol Ther · April 1994 BACKGROUND: Fluorinated ether anesthetic hepatotoxicity and nephrotoxicity are mediated by cytochrome P450-catalyzed oxidative metabolism. Metabolism of the volatile anesthetic enflurane to inorganic fluoride ion by human liver microsomes in vitro is catal ... Full text Link to item Cite

Identification of cytochrome P450 2E1 as the predominant enzyme catalyzing human liver microsomal defluorination of sevoflurane, isoflurane, and methoxyflurane.

Journal Article Anesthesiology · October 1993 BACKGROUND: Renal and hepatic toxicity of the fluorinated ether volatile anesthetics is caused by biotransformation to toxic metabolites. Metabolism also contributes significantly to the elimination pharmacokinetics of some volatile agents. Although innume ... Full text Link to item Cite

Single-dose disulfiram inhibition of chlorzoxazone metabolism: a clinical probe for P450 2E1.

Journal Article Clin Pharmacol Ther · June 1993 Disulfiram and its reduced metabolite diethyldithiocarbamate have been identified previously as selective mechanism-based inhibitors of human liver microsomal cytochrome P450 2E1 in vitro. In animals, a single oral dose of disulfiram has been shown to prod ... Full text Link to item Cite

Human alfentanil metabolism by cytochrome P450 3A3/4. An explanation for the interindividual variability in alfentanil clearance?

Journal Article Anesth Analg · May 1993 Alfentanil undergoes extensive hepatic metabolism and exhibits a high degree of interindividual variability in hepatic clearance. The purpose of this investigation was to determine the specific hepatic cytochrome P450 isozyme(s) that catalyzes alfentanil m ... Full text Link to item Cite

Human liver microsomal enflurane defluorination catalyzed by cytochrome P-450 2E1.

Journal Article Drug Metab Dispos · 1993 The volatile anesthetic agent enflurane undergoes oxidative metabolism in human liver, yielding both inorganic and organic fluoride metabolites. Numerous studies conducted in animals indicate that the enzyme cytochrome P-450 2E1 is a major catalyst for the ... Link to item Cite

Metabolism of ketamine stereoisomers by human liver microsomes.

Journal Article Anesthesiology · December 1992 Ketamine is used clinically as a racemic mixture of optical isomers that differ in their analgesic properties and psychomimetic effects. Administered individually, or together as the racemate, ketamine enantiomers differ in their hepatic clearance and dura ... Full text Link to item Cite

Ketamine as a probe for medetomidine stereoisomer inhibition of human liver microsomal drug metabolism.

Journal Article Anesthesiology · December 1992 Medetomidine (MED) is a novel, selective, alpha 2 adrenergic agonist with potent sedative, hypnotic, and analgesic properties, currently undergoing evaluation as an anesthetic adjuvant. The pharmacologic effects of MED are stereospecific, due entirely to t ... Full text Link to item Cite

Angioedema of the tongue--cause?

Journal Article Anesth Analg · October 1992 Full text Link to item Cite

Chronic epidural bupivacaine-opioid infusion in intractable cancer pain.

Journal Article Pain · June 1992 This study examined the efficacy and toxicity associated with chronic epidural opioid-bupivacaine infusions. In a series of 68 patients with cancer pain refractory to epidural opioids alone, analgesia was effectively regained by infusing a opioid-bupivacai ... Full text Link to item Cite

Influence of dexmedetomidine and clonidine on human liver microsomal alfentanil metabolism.

Journal Article Anesthesiology · September 1991 Perioperative administration of the alpha 2 agonist clonidine has been shown to increase plasma alfentanil concentrations; however, the mechanism for this pharmacokinetic drug interaction is unknown. Because alfentanil undergoes extensive hepatic biotransf ... Full text Link to item Cite

Aerosol propellant interference with clinical mass spectrometers.

Journal Article J Clin Monit · April 1991 Metered dose inhalers containing halogenated propellants may interfere with mass spectrometer quantitation of halogenated inhalation anesthetics. We identify the propellant(s) in a commercially available metered dose inhaler that caused erroneous mass spec ... Full text Link to item Cite

Hypokalemia before induction of anesthesia and prevention by beta 2 adrenoceptor antagonism.

Journal Article Anesth Analg · February 1991 We have observed that serum potassium levels measured immediately before induction of anesthesia ("preinduction K+") are often lower than those measured 1-3 days preoperatively ("preoperative K+"). The purpose of this investigation was to determine, in two ... Full text Link to item Cite

Reply

Journal Article Canadian Journal of Anaesthesia · May 1, 1990 Full text Cite

Atrial natriuretic factor and cardiopulmonary bypass (I: Reply)

Journal Article Canadian Journal of Anaesthesia · January 1, 1990 Cite

Errata

Journal Article Canadian Journal of Anaesthesia · January 1, 1990 Full text Cite

Lack of effect of cimetidine on acetaminophen disposition in humans.

Journal Article Clin Pharmacol Ther · November 1989 The effect of cimetidine administration on the disposition of acetaminophen was evaluated in seven men and six women. One gram of acetaminophen was administered to each volunteer after an overnight fast on two occasions in a balanced crossover design with ... Full text Link to item Cite

Influence of hypothermic cardiopulmonary bypass on atrial natriuretic factor levels.

Journal Article Can J Anaesth · September 1989 Atrial natriuretic factor (ANF) is a peptide released from the heart in response to atrial distension. This peptide causes diuresis, vasodilatation, decreased blood pressure, and antagonizes the renin-aldosterone and antidiuretic hormone neuraxes. The infl ... Full text Link to item Cite

Atrial natriuretic factor may mediate the renal effects of PEEP ventilation.

Journal Article Anesthesiology · December 1988 Mechanical ventilation with PEEP decreases urine output and urinary sodium excretion. Observed changes in cardiac output, renal blood flow, renin release, and antidiuretic hormone (ADH) secretion do not adequately explain the renal effects of PEEP. Altered ... Full text Link to item Cite

Nitrofurantoin-stimulated proteolysis in human erythrocytes: a novel index of toxic insult by nitroaromatics.

Journal Article J Pharmacol Exp Ther · November 1988 Nitrofurantoin is an antimicrobial agent that causes nonimmune hemolytic anemia in susceptible populations and produces oxidant stress and cellular damage by mechanisms that differ from those associated with oxidants such as phenylhydrazine, which has been ... Link to item Cite

Left ventricular free wall rupture in acute myocardial infarction-a spectrum of severity

Journal Article Journal of Cardiothoracic Anesthesia · January 1, 1988 Full text Cite

Anthracenedione antineoplastic agent effects on drug metabolism in vitro and in vivo: relationship between structure and mechanism of inhibition.

Journal Article Fundam Appl Toxicol · July 1987 Two anthracenedione antineoplastic agents, mitoxantrone and the nonhydroxylated analog, ametantrone, were found to inhibit hepatic microsomal cytochrome P-450-dependent drug metabolism in vitro and in vivo. Ethoxycoumarin deethylase activity of phenobarbit ... Full text Link to item Cite

Mitoxantrone and ametantrone inhibit hydroperoxide-dependent initiation and propagation reactions in fatty acid peroxidation.

Journal Article J Biol Chem · September 5, 1985 The anthracenedione antineoplastic agents mitoxantrone and ametantrone are potent inhibitors of basal and drug-stimulated lipid peroxidation in a variety of subcellular systems (Kharasch, E. D., and Novak, R. F. (1983) J. Pharmacol. Exp. Ther. 226, 500-506 ... Link to item Cite

Mitoxantrone: propensity for free radical formation and lipid peroxidation--implications for cardiotoxicity.

Journal Article Invest New Drugs · 1985 Results of comparative studies on stimulation of the rates of cofactor consumption, superoxide generation and hydrogen peroxide production by mitoxantrone (Novantrone; dihydroxyanthracenedione; MXN), ametantrone (AM), doxorubicin (DOX) and daunorubicin (DN ... Full text Link to item Cite

Spectroscopic evidence for anthracenedione antineoplastic agent self-association and complex formation with flavin nucleotides.

Journal Article Arch Biochem Biophys · November 1, 1984 Dihydroxyanthraquinone (DHAQ) and ametantrone (anthraquinone) are two new anthracenedione antineoplastic agents which were found by proton NMR spectroscopy to self-associate in aqueous media. Self-association was consistent with a bimolecular model, with a ... Full text Link to item Cite

Inhibitory effects of anthracenedione antineoplastic agents on hepatic and cardiac lipid peroxidation.

Journal Article J Pharmacol Exp Ther · August 1983 The effects of mitoxantrone, ametantrone and a monohydroxylated anthracenedione on hepatic microsomal, cardiac sarcosomal and cardiac mitochondrial lipid peroxidation were examined and compared with those of doxorubicin and daunorubicin. Rabbit microsomal ... Link to item Cite

Bis(alkylamino)anthracenedione antineoplastic agent metabolic activation by NADPH-cytochrome P-450 reductase and NADH dehydrogenase: diminished activity relative to anthracyclines.

Journal Article Arch Biochem Biophys · July 15, 1983 Stimulation of the rates of NAD(P)H oxidation, superoxide generation, and hydrogen peroxide formation by three anthracenedione antineoplastic agents in the presence of NADPH-cytochrome P-450 reductase, NADH dehydrogenase, or rabbit hepatic microsomes was s ... Full text Link to item Cite

Inhibition of microsomal oxidative drug metabolism by 1,4-bis (2-[(2-hydroxyethyl)amino]-ethylamino)-9,10-anthracenedione diacetate, a new antineoplastic agent.

Journal Article Mol Pharmacol · September 1982 The effects of 1,4-bis(2-[(2-hydroxyethyl)amino]-ethylamino)-9,10-anthracenedione diacetate (HAQ) on rabbit liver microsomal oxidative drug metabolism were investigated. HAQ was found to inhibit O-dealkylase and N-demethylase activities in phenobarbital-in ... Link to item Cite

Anthracenedione antineoplastic agent inhibition of microsomal drug metabolism

Journal Article Federation Proceedings · January 1, 1982 Cite

Intracellular magnesium does not antagonize calcium-dependent acetylcholine secretion.

Journal Article J Physiol · May 1981 1. The effects of intracellular application of Ca and Mg ions on evoked acetylcholine secretion at frog motor nerve terminals were studied. Ca and Mg were applied to the nerve-ending cytoplasm using liposomes as a vehicle. 2. Under conditions in which intr ... Full text Link to item Cite

31P FT NMR analysis of adriamycin-induced alteration in cardiac energy metabolism

Journal Article Federation Proceedings · January 1, 1979 Cite