Scholars@Duke
Daniel Gonzalez

Daniel Gonzalez

Associate Professor in Medicine
Medicine, Clinical Pharmacology
daniel.gonzalez@duke.edu
P.O. Box 17969, Duke Clinical Reserach Institute, Durham, NC 27715
300 W. Morgan Street, Durham, NC 27701

Selected Publications

Physiologically-Based Pharmacokinetic Modeling of Total and Unbound Valproic Acid to Evaluate Dosing in Children With and Without Hypoalbuminemia.

Journal Article Clin Pharmacokinet · September 19, 2024 BACKGROUND AND OBJECTIVE: Valproic acid (VPA) demonstrates nonlinear pharmacokinetics (PK) due to a capacity-limited protein binding, which has potential implications on its total and unbound plasma concentrations, especially during hypoalbuminemia. A phys ... Full text Link to item Cite

Evaluation of Obesity-Related Physiological Changes on Pantoprazole Clearance in Children Using a Population Pharmacokinetic Approach.

Journal Article J Clin Pharmacol · August 27, 2024 Pediatric obesity is a growing health concern, affecting millions of children worldwide. While pharmacokinetic (PK) changes in numerous commonly prescribed medications have been linked to obesity, the physiological mechanisms driving these alterations and ... Full text Link to item Cite

Pharmacokinetics of Dexamethasone in Children and Adolescents with Obesity.

Journal Article J Clin Pharmacol · August 9, 2024 Dexamethasone is a synthetic glucocorticoid approved for treating disorders of various organ systems in both adult and pediatric populations. Currently, approved pediatric dosing recommendations are weight-based, but it is unknown whether differences in de ... Full text Link to item Cite

Using Real-World Data to Externally Evaluate Population Pharmacokinetic Models of Dexmedetomidine in Children and Infants.

Journal Article Journal of clinical pharmacology · August 2024 Dexmedetomidine is a sedative used in both adults and off-label in children with considerable reported pharmacokinetic (PK) interindividual variability affecting drug exposure across populations. Several published models describe the population PKs of dexm ... Full text Cite

Physiologically-based pharmacokinetic modeling of pantoprazole to evaluate the role of CYP2C19 genetic variation and obesity in the pediatric population.

Journal Article CPT Pharmacometrics Syst Pharmacol · August 2024 Pantoprazole is a proton pump inhibitor indicated for the treatment of gastroesophageal reflux disease, a condition that disproportionately affects children with obesity. Appropriately dosing pantoprazole in children with obesity requires understanding the ... Full text Link to item Cite

Characterizing Enoxaparin's Population Pharmacokinetics to Guide Dose Individualization in the Pediatric Population.

Journal Article Clin Pharmacokinet · July 2024 BACKGROUND AND OBJECTIVE: Pediatric dosing of enoxaparin was derived based on extrapolation of the adult therapeutic range to children. However, a large fraction of children do not achieve therapeutic anticoagulation with initial dosing. We aim to use real ... Full text Link to item Cite

Indomethacin Pharmacokinetics and Pharmacodynamics in Pregnancies With Preterm Labor: The Need for Dose-Ranging Trials.

Journal Article J Clin Pharmacol · June 2024 The use of indomethacin to delay delivery in preterm labor (PTL) is widely accepted; however, the optimal dosage of indomethacin in pregnancy is unknown. Here, we perform population pharmacokinetic (PK) and pharmacodynamic (PD) analyses, characterize the p ... Full text Link to item Cite

Application of Physiologically Based Pharmacokinetic Modeling to Characterize the Effects of Age and Obesity on the Disposition of Levetiracetam in the Pediatric Population.

Journal Article Clin Pharmacokinet · June 2024 BACKGROUND: Levetiracetam is an antiseizure medication used for several seizure types in adults and children aged 1 month and older; however, due to a lack of data, pharmacokinetic (PK) variability of levetiracetam is not adequately characterized in certai ... Full text Link to item Cite

A phase I trial of caffeine to evaluate safety in infants with hypoxic-ischemic encephalopathy.

Journal Article J Perinatol · April 2024 OBJECTIVE: Caffeine provides neuroprotection following hypoxic-ischemic injury in animals. We characterized the safety of escalating doses of caffeine in infants with hypoxic-ischemic encephalopathy (HIE) receiving therapeutic hypothermia. STUDY DESIGN: Ph ... Full text Link to item Cite

Sources of pharmacokinetic and pharmacodynamic variability and clinical pharmacology studies of antiseizure medications in the pediatric population.

Journal Article Clin Transl Sci · April 2024 Multiple treatment options exist for children with epilepsy, including surgery, dietary therapies, neurostimulation, and antiseizure medications (ASMs). ASMs are the first line of therapy, and more than 30 ASMs have U.S. Food and Drug Administration (FDA) ... Full text Link to item Cite

Abatacept Pharmacokinetics and Exposure Response in Patients Hospitalized With COVID-19: A Secondary Analysis of the ACTIV-1 IM Randomized Clinical Trial.

Journal Article JAMA Netw Open · April 1, 2024 IMPORTANCE: The pharmacokinetics of abatacept and the association between abatacept exposure and outcomes in patients with severe COVID-19 are unknown. OBJECTIVE: To characterize abatacept pharmacokinetics, relate drug exposure with clinical outcomes, and ... Full text Link to item Cite

Population Pharmacokinetics of Caffeine in Neonates with Congenital Heart Disease and Associations with Acute Kidney Injury.

Journal Article J Clin Pharmacol · March 2024 Cardiac surgery-associated acute kidney injury (CS-AKI) occurs in approximately 65% of neonates undergoing cardiac surgery on cardiopulmonary bypass and contributes to morbidity and mortality. Caffeine may reduce CS-AKI by counteracting adenosine receptor ... Full text Link to item Cite

Population Pharmacokinetics and Model-Based Dose Optimization of Vancomycin in Sudanese Adult Patients with Renal Impairment.

Journal Article Drug design, development and therapy · January 2024 PurposeThe study aimed to perform a population pharmacokinetic (PK) analysis to obtain vancomycin PK parameter estimates in Sudanese adult patients. The population PK model is then applied to perform model-based dose optimization.Patients and ... Full text Cite

Dabigatran Dosing Proposal for Adults With Atrial Fibrillation: Stress-Testing Renal Function Range in Real World Patients.

Journal Article Clin Pharmacol Ther · August 2023 Dabigatran is the first of four direct-acting oral anticoagulants approved to prevent stroke in adult patients with atrial fibrillation using a fixed two-dose scheme compared with warfarin dosing adjusted to a prothrombin time range associated with optimal ... Full text Link to item Cite

Leveraging physiologically based pharmacokinetic modeling to optimize dosing for lopinavir/ritonavir with rifampin in pediatric patients.

Journal Article Pharmacotherapy · July 2023 STUDY OBJECTIVE: Treatment of HIV and tuberculosis co-infection leads to significant mortality in pediatric patients, and treatment can be challenging due to the clinically significant drug-drug interaction (DDI) between lopinavir/ritonavir (LPV/RTV) and r ... Full text Link to item Cite

Population Pharmacokinetics of Posaconazole in Immune-Compromised Children and Assessment of Target Attainment in Invasive Fungal Disease.

Journal Article Clin Pharmacokinet · July 2023 BACKGROUND AND OBJECTIVE: Posaconazole (PSZ) is a triazole antifungal for the management of invasive fungal disease (IFD) in adults and children. Although PSZ is available as an intravenous (IV) solution, oral suspension (OS) and delayed-release tablets (D ... Full text Link to item Cite

Association between simulated ketamine exposures and oxygen saturations in children.

Journal Article Int J Pharmacokinet · February 2023 AIM: We performed a real-world data analysis to evaluate the relationship between simulated ketamine exposures and oxygen desaturation in children. MATERIALS & METHODS: A previously developed population pharmacokinetic model was used to simulate exposures ... Full text Open Access Link to item Cite

Extrapolation of Adult Efficacy Data to Pediatric Systemic Lupus Erythematosus: Evaluating Similarities in Exposure-Response.

Journal Article J Clin Pharmacol · January 2023 To streamline drug development, the United States Food and Drug Administration (FDA) can consider the extrapolation of adult efficacy data to children when the disease and drug effects are sufficiently similar. This study explored whether the relationship ... Full text Link to item Cite

Effects of obesity on the pharmacology of proton pump inhibitors: current understanding and future implications for patient care and research.

Journal Article Expert Opin Drug Metab Toxicol · January 2023 INTRODUCTION: In the United States, obesity affects approximately ⅖ adults and ⅕ children, leading to increased risk for comorbidities, like gastroesophageal reflux disease (GERD), treated increasingly with proton pump inhibitors (PPIs). Currently, there a ... Full text Link to item Cite

Leveraging a Previously Published Population Pharmacokinetic Model to Predict Rivaroxaban Exposure in Real-World Patients.

Journal Article J Clin Pharmacol · December 2022 Population pharmacokinetic (PK)/pharmacodynamic models are commonly used to inform drug dosing; however, often real-world patients are not well represented in the clinical trial population. We sought to determine how well dosing recommended in the rivaroxa ... Full text Link to item Cite

Pharmacokinetics of hydroxychloroquine in paediatric lupus: data from a novel, direct-to-family clinical trial.

Journal Article Lupus Sci Med · November 2022 OBJECTIVE: Determine the pharmacokinetics (PK) and exposure-response of hydroxychloroquine (HCQ) and desethylhydroxychloroquine (DHCQ) in paediatric SLE (pSLE). METHODS: We conducted an exploratory phase 2, direct-to-family trial. Children enrolled in the ... Full text Link to item Cite

Machine learning-guided covariate selection for time-to-event models developed from a small sample of real-world patients receiving bevacizumab treatment.

Journal Article CPT Pharmacometrics Syst Pharmacol · October 2022 Therapeutic outcomes in patients with metastatic colorectal cancer (mCRC) receiving bevacizumab treatment are highly variable, and a reliable predictive factor is not available. Progression-free survival (PFS) and overall survival (OS) were recorded from a ... Full text Link to item Cite

Use of Real-World Data and Physiologically-Based Pharmacokinetic Modeling to Characterize Enoxaparin Disposition in Children With Obesity.

Journal Article Clin Pharmacol Ther · August 2022 Dosing guidance for children with obesity is often unknown despite the fact that nearly 20% of US children are classified as obese. Enoxaparin, a commonly prescribed low-molecular-weight heparin, is dosed based on body weight irrespective of obesity status ... Full text Link to item Cite

Physiologically Based Pharmacokinetic Modeling of Metformin in Children and Adolescents With Obesity.

Journal Article J Clin Pharmacol · August 2022 Childhood obesity continues to rise in the United States and, with it, the off-label use of metformin for weight loss. The influence of age and obesity on the drug's disposition and exposure has not previously been studied using a mechanistic framework. He ... Full text Link to item Cite

Use of physiologically-based pharmacokinetic modeling to inform dosing of the opioid analgesics fentanyl and methadone in children with obesity.

Journal Article CPT Pharmacometrics Syst Pharmacol · June 2022 Obesity is an increasingly alarming public health threat, with nearly 20% of children classified as obese in the United States today. Children with obesity are commonly prescribed the opioids fentanyl and methadone, and accurate dosing is critical to reduc ... Full text Link to item Cite

The relationship between simulated milrinone exposure and hypotension in children.

Journal Article Cardiol Young · May 2022 INTRODUCTION: Hypotension is an adverse event that may be related to systemic exposure of milrinone; however, the true exposure-safety relationship is unknown. METHODS: Using the Pediatric Trials Network multicentre repository, we identified children ≤17 y ... Full text Link to item Cite

Gaps in Hepatitis A and Hepatitis B Vaccination among Hepatitis C Antibody-Positive Individuals Experiencing Homelessness

Journal Article Open Forum Infectious Diseases · May 1, 2022 Vaccination for both hepatitis A (HAV) and hepatitis B (HBV) is recommended in hepatitis C infection (HCV). Among HCV antibody-positive persons experiencing homelessness, we identified high rates of HAV (34%) and HBV vaccine (35%) eligibility, highlighting ... Full text Cite

Development and Evaluation of a Virtual Population of Children with Obesity for Physiologically Based Pharmacokinetic Modeling.

Journal Article Clin Pharmacokinet · February 2022 BACKGROUND AND OBJECTIVE: While one in five children in the USA are now obese, and more than three-quarters receive at least one drug during childhood, there is limited dosing guidance for this vulnerable patient population. Physiologically based pharmacok ... Full text Link to item Cite

Physiologically-based pharmacokinetic modeling of oxcarbazepine and levetiracetam during adjunctive antiepileptic therapy in children and adolescents.

Journal Article CPT Pharmacometrics Syst Pharmacol · February 2022 Oxcarbazepine (OXZ) and levetiracetam (LEV) are two new generation anti-epileptic drugs, often co-administered in children with enzyme-inducing antiepileptic drugs (EIAEDs). The anti-epileptic effect of OXZ and LEV are linked to the exposure of OXZ's activ ... Full text Link to item Cite

Safety of sildenafil in extremely premature infants: a phase I trial.

Journal Article J Perinatol · January 2022 OBJECTIVE: To characterize the safety of sildenafil in premature infants. STUDY DESIGN: A phase I, open-label trial of sildenafil in premature infants receiving sildenafil per usual clinical care (cohort 1) or receiving a single IV dose of sildenafil (coho ... Full text Link to item Cite

Hydroxychloroquine PK and exposure-response in pregnancies with lupus: the importance of adherence for neonatal outcomes.

Journal Article Lupus Sci Med · January 2022 OBJECTIVE: Evaluate the impact of pregnancy physiology and medication non-adherence on serum hydroxychloroquine (HCQ) pharmacokinetics (PK) and exposure-response in SLE. METHODS: We conducted a PK analysis using data from two observational pregnancy regist ... Full text Link to item Cite

Characterizing Pharmacokinetics in Children With Obesity-Physiological, Drug, Patient, and Methodological Considerations.

Journal Article Front Pharmacol · 2022 Childhood obesity is an alarming public health problem. The pediatric obesity rate has quadrupled in the past 30 years, and currently nearly 20% of United States children and 9% of children worldwide are classified as obese. Drug distribution and eliminati ... Full text Link to item Cite

External Evaluation of Risperidone Population Pharmacokinetic Models Using Opportunistic Pediatric Data.

Journal Article Front Pharmacol · 2022 Risperidone is approved to treat schizophrenia in adolescents and autistic disorder and bipolar mania in children and adolescents. It is also used off-label in younger children for various psychiatric disorders. Several population pharmacokinetic models of ... Full text Link to item Cite

Physiologically Based Pharmacokinetic Modeling of Meropenem in Preterm and Term Infants.

Conference Clin Pharmacokinet · December 2021 BACKGROUND: Meropenem is a broad-spectrum carbapenem antibiotic approved by the US Food and Drug Administration for use in pediatric patients, including treating complicated intra-abdominal infections in infants < 3 months of age. The impact of maturation ... Full text Link to item Cite

Pharmacokinetics of perioperative FVIII in adult patients with haemophilia A: An external validation and development of an alternative population pharmacokinetic model.

Journal Article Haemophilia · November 2021 INTRODUCTION: Haemophilia A patients require perioperative clotting factor replacement to limit excessive bleeding. Weight-based dosing of Factor VIII (FVIII) does not account for inter-individual pharmacokinetic (PK) variability, and may lead to suboptima ... Full text Link to item Cite

Leveraging Physiologically Based Pharmacokinetic Modeling and Experimental Data to Guide Dosing Modification of CYP3A-Mediated Drug-Drug Interactions in the Pediatric Population.

Journal Article Drug Metab Dispos · September 2021 Solithromycin is a novel fluoroketolide antibiotic that is both a substrate and time-dependent inhibitor of CYP3A. Solithromycin has demonstrated efficacy in adults with community-acquired bacterial pneumonia and has also been investigated in pediatric pat ... Full text Link to item Cite

External Evaluation of Two Pediatric Population Pharmacokinetics Models of Oral Trimethoprim and Sulfamethoxazole.

Journal Article Antimicrob Agents Chemother · June 17, 2021 The antibiotic combination trimethoprim (TMP)-sulfamethoxazole (SMX) has a broad spectrum of activity and is used for the treatment of numerous infections, but pediatric pharmacokinetic (PK) data are limited. We previously published population PK (popPK) m ... Full text Link to item Cite

Pediatric Drug-Drug Interaction Evaluation: Drug, Patient Population, and Methodological Considerations.

Journal Article J Clin Pharmacol · June 2021 Hospitalized pediatric patients and those with complex or chronic conditions treated on an outpatient basis are commonly prescribed multiple drugs, resulting in increased risk for drug-drug interactions (DDIs). Although dedicated DDI evaluations are routin ... Full text Link to item Cite

Association between Nephrotoxic Drug Combinations and Acute Kidney Injury in the Neonatal Intensive Care Unit.

Journal Article J Pediatr · January 2021 OBJECTIVE: To determine the incidence of acute kidney injury (AKI) in infants exposed to nephrotoxic drug combinations admitted to 268 neonatal intensive care units managed by the Pediatrix Medical Group. STUDY DESIGN: We included infants born at 22-36 wee ... Full text Link to item Cite

Physiologically-Based Pharmacokinetic Modeling Characterizes the CYP3A-Mediated Drug-Drug Interaction Between Fluconazole and Sildenafil in Infants.

Journal Article Clin Pharmacol Ther · January 2021 Physiologically-based pharmacokinetic (PBPK) modeling can potentially predict pediatric drug-drug interactions (DDIs) when clinical DDI data are limited. In infants for whom treatment of pulmonary hypertension and prevention or treatment of invasive candid ... Full text Link to item Cite

Low etanercept concentrations in children with obesity and juvenile idiopathic arthritis

Journal Article Journal of Pediatric Pharmacology and Therapeutics · January 1, 2021 OBJECTIVE To evaluate the impact of obesity on etanercept (ETN) drug exposure in children with juvenile idiopathic arthritis (JIA). METHODS We conducted a pilot, cross-sectional, observational study in a real-world cohort of children with JIA receiving ETN ... Full text Cite

Creatinine-Based Renal Function Assessment in Pediatric Drug Development: An Analysis Using Clinical Data for Renally Eliminated Drugs.

Journal Article Clin Pharmacol Ther · January 2021 The estimated glomerular filtration rate (eGFR) equations based on serum creatinine (SCR) have been used for pediatric dose adjustment in drug labeling. This study evaluated the performance of those equations in estimating individual clearance of drugs tha ... Full text Link to item Cite

Supporting Precision Dosing in Drug Labeling.

Journal Article Clin Pharmacol Ther · January 2021 Full text Link to item Cite

Population Pharmacokinetics of Metoclopramide in Infants, Children, and Adolescents.

Journal Article Clin Transl Sci · November 2020 Metoclopramide is commonly used for gastroesophageal reflux. The aims of the present study were to develop a pediatric population pharmacokinetic (PopPK) model, which was applied to simulate the metoclopramide exposure following dosing used in clinical pra ... Full text Link to item Cite

Dr. Balevic, et al reply.

Journal Article J Rheumatol · October 1, 2020 Full text Link to item Cite

Simulated Assessment of Pharmacokinetically Guided Dosing for Investigational Treatments of Pediatric Patients With Coronavirus Disease 2019.

Journal Article JAMA Pediatr · October 1, 2020 IMPORTANCE: Children of all ages appear susceptible to severe acute respiratory syndrome coronavirus 2 infection. To support pediatric clinical studies for investigational treatments of coronavirus disease 2019 (COVID-19), pediatric-specific dosing is requ ... Full text Link to item Cite

Rivaroxaban Precision Dosing Strategy for Real-World Atrial Fibrillation Patients.

Journal Article Clin Transl Sci · July 2020 Rivaroxaban is a direct-acting oral anticoagulant approved to prevent strokes in patients with atrial fibrillation. Dosage recommendations are approved for all adult patients to receive either 15 mg or 20 mg once daily depending upon renal function. There ... Full text Link to item Cite

Hydroxychloroquine in Patients with Rheumatic Disease Complicated by COVID-19: Clarifying Target Exposures and the Need for Clinical Trials.

Journal Article J Rheumatol · May 11, 2020 OBJECTIVE: To characterize hydroxychloroquine (HCQ) exposure in patients with rheumatic disease receiving longterm HCQ compared to target concentrations with reported antiviral activity against the coronavirus disease 2019 caused by SARS-CoV-2 (COVID-19). ... Full text Link to item Cite

Translational Approach to Predicting the Efficacy of Maraviroc-Based Regimens as HIV Preexposure Prophylaxis.

Journal Article Antimicrob Agents Chemother · January 27, 2020 Maraviroc-based regimens have been explored as preexposure prophylaxis (PrEP) against human immunodeficiency virus (HIV). In this study, we utilized mucosal tissue drug exposure data, combined with target concentrations generated in vitro, in a pharmacokin ... Full text Link to item Cite

Precision Dosing Priority Criteria: Drug, Disease, and Patient Population Variables.

Journal Article Front Pharmacol · 2020 The administered dose of a drug modulates whether patients will experience optimal effectiveness, toxicity including death, or no effect at all. Dosing is particularly important for diseases and/or drugs where the drug can decrease severe morbidity or prol ... Full text Link to item Cite

Population Pharmacokinetics of Milrinone in Infants, Children, and Adolescents.

Journal Article J Clin Pharmacol · December 2019 Milrinone is a type 3 phosphodiesterase inhibitor used to improve cardiac output in critically ill infants and children. Milrinone is primarily excreted unchanged in the urine, raising concerns for toxic accumulation in the setting of renal dysfunction of ... Full text Link to item Cite

A Dried Blood Spot Analysis for Solithromycin in Adolescents, Children, and Infants: A Short Communication.

Journal Article Ther Drug Monit · December 2019 BACKGROUND: Solithromycin is a fourth-generation macrolide antibiotic with potential efficacy in pediatric community-acquired bacterial pneumonia. Pharmacokinetic (PK) studies of solithromycin in pediatric subjects are limited, therefore application of min ... Full text Link to item Cite

Population pharmacokinetics of sildenafil in extremely premature infants.

Journal Article Br J Clin Pharmacol · December 2019 AIMS: To characterize the population pharmacokinetics (PK) of sildenafil and its active metabolite, N-desmethyl sildenafil (DMS), in premature infants. METHODS: We performed a multicentre, open-label trial to characterize the PK of sildenafil in infants ≤2 ... Full text Link to item Cite

Population Pharmacokinetic/Pharmacodynamic Modeling of Methylprednisolone in Neonates Undergoing Cardiopulmonary Bypass.

Journal Article CPT Pharmacometrics Syst Pharmacol · December 2019 Methylprednisolone is used in neonates to modulate cardiopulmonary bypass (CPB)-induced inflammation, but optimal dosing and exposure are unknown. We used plasma methylprednisolone and interleukin (IL)-6 and IL-10 concentrations from neonates enrolled in a ... Full text Link to item Cite

β2 -Adrenergic Receptor Gene Affects the Heart Rate Response of β-Blockers: Evidence From 3 Clinical Studies.

Journal Article J Clin Pharmacol · November 2019 β-Blockers' heart rate (HR)-lowering effect is an important determinant of the effectiveness for this class of drugs, yet it is variable among β-blocker-treated patients. To date, genetic studies have revealed several genetic signals associated with HR res ... Full text Link to item Cite

Physiologically-Based Pharmacokinetic Modeling of Fluconazole Using Plasma and Cerebrospinal Fluid Samples From Preterm and Term Infants.

Conference CPT Pharmacometrics Syst Pharmacol · July 2019 Fluconazole is used to treat hematogenous Candida meningoencephalitis in preterm and term infants. To characterize plasma and central nervous system exposure, an adult fluconazole physiologically-based pharmacokinetic (PBPK) model was scaled to infants, ac ... Full text Link to item Cite

The Population Pharmacokinetics of High-Dose Methotrexate in Infants with Acute Lymphoblastic Leukemia Highlight the Need for Bedside Individualized Dose Adjustment: A Report from the Children's Oncology Group.

Journal Article Clin Pharmacokinet · July 2019 BACKGROUND: Infants with acute lymphoblastic leukemia (ALL) treated with high-dose methotrexate may have reduced methotrexate clearance (CL) due to renal immaturity, which may predispose them to toxicity. OBJECTIVE: The aim of this study was to develop a p ... Full text Link to item Cite

Assessing CYP2C19 Ontogeny in Neonates and Infants Using Physiologically Based Pharmacokinetic Models: Impact of Enzyme Maturation Versus Inhibition.

Journal Article CPT Pharmacometrics Syst Pharmacol · March 2019 The objective of this study was to develop pediatric physiologically based pharmacokinetic (PBPK) models for pantoprazole and esomeprazole. Pediatric PBPK models were developed by Simcyp version 15 by incorporating cytochrome P450 (CYP)2C19 maturation and ... Full text Link to item Cite

Can they imagine the future? A qualitative study exploring the skills employers seek in pharmaceutical sciences doctoral graduates.

Journal Article PLoS One · 2019 Concerns about the extent to which graduate programs adequately prepare students for the workplace have prompted numerous calls for reform. Understanding what employers look for in doctoral graduates can help schools better align graduate training with wor ... Full text Link to item Cite

Pharmacokinetics of Ceftaroline in a Preterm Infant With Methicillin-Resistant Staphylococcus Aureus Pneumonia.

Journal Article J Pediatric Infect Dis Soc · December 3, 2018 We report here the first pharmacokinetic-pharmacodynamic relationship for ceftaroline in a preterm infant born at <28 weeks' gestational age who was given ceftaroline (8.5 mg/kg every 8 hours) for pneumonia attributable to methicillin-resistant Staphylocco ... Full text Link to item Cite

Evaluation of Gentamicin Exposure in the Neonatal Intensive Care Unit and Hearing Function at Discharge.

Journal Article J Pediatr · December 2018 OBJECTIVE: To characterize the association between gentamicin dosing, duration of treatment, and ototoxicity in hospitalized infants. STUDY DESIGN: This retrospective cohort study conducted at 330 neonatal intensive care units (2002-2014) included inborn i ... Full text Link to item Cite

Population Pharmacokinetics and Exploratory Exposure-Response Relationships of Diazepam in Children Treated for Status Epilepticus.

Journal Article CPT Pharmacometrics Syst Pharmacol · November 2018 Diazepam is labeled for status epilepticus (SE) in children, but there are limited data characterizing its disposition in pediatric patients. We developed a population pharmacokinetic (PK) model of i.v. diazepam in children with SE. We evaluated relationsh ... Full text Link to item Cite

External Evaluation of a Gentamicin Infant Population Pharmacokinetic Model Using Data from a National Electronic Health Record Database.

Journal Article Antimicrob Agents Chemother · September 2018 Gentamicin is a common antibiotic used in neonates and infants. A recently published population pharmacokinetic (PK) model was developed using data from multiple studies, and the objective of our analyses was to evaluate the feasibility of using a national ... Full text Link to item Cite

Clinical pharmacology considerations for children supported with ventricular assist devices.

Journal Article Cardiol Young · September 2018 The ventricular assist device is being increasingly used as a "bridge-to-transplant" option in children with heart failure who have failed medical management. Care for this medically complex population must be optimised, including through concomitant pharm ... Full text Link to item Cite

Population Pharmacokinetics of Intramuscular and Intravenous Ketamine in Children.

Journal Article J Clin Pharmacol · August 2018 Ketamine is an N-methyl D-aspartate receptor antagonist used off-label to facilitate dissociative anesthesia in children undergoing invasive procedures. Available for both intravenous and intramuscular administration, ketamine is commonly used when vascula ... Full text Link to item Cite

Population Pharmacokinetics and Safety of Solithromycin following Intravenous and Oral Administration in Infants, Children, and Adolescents.

Journal Article Antimicrob Agents Chemother · August 2018 Solithromycin is a novel fluoroketolide antibiotic which was under investigation for the treatment of community-acquired bacterial pneumonia (CABP). A phase 1 study was performed to characterize the pharmacokinetics (PK) and safety of solithromycin in chil ... Full text Link to item Cite

Challenges and Solutions for Future Pharmacy Practice in the Era of Precision Medicine.

Journal Article Am J Pharm Educ · August 2018 As precision medicine research and its clinical applications continue to advance, it is critical for pharmacists to be involved in these developments to deliver optimal, tailored drug therapies for patients. To ensure pharmacists remain leaders in the fiel ... Full text Link to item Cite

Improving Pediatric Protein Binding Estimates: An Evaluation of α1-Acid Glycoprotein Maturation in Healthy and Infected Subjects.

Journal Article Clin Pharmacokinet · May 2018 BACKGROUND: Differences in plasma protein levels observed between children and adults can alter the extent of xenobiotic binding in plasma, resulting in divergent patterns of exposure. OBJECTIVE: This study aims to quantify the ontogeny of α1-acid glycopro ... Full text Link to item Cite

Genome-Wide Association Approach Identified Novel Genetic Predictors of Heart Rate Response to β-Blockers.

Journal Article J Am Heart Assoc · February 24, 2018 BACKGROUND: For many indications, the negative chronotropic effect of β-blockers is important to their efficacy, yet the heart rate (HR) response to β-blockers varies. Herein, we sought to use a genome-wide association approach to identify novel single nuc ... Full text Link to item Cite

Association between oral sildenafil dosing, predicted exposure, and systemic hypotension in hospitalised infants.

Journal Article Cardiol Young · January 2018 BACKGROUND: The relationship between sildenafil dosing, exposure, and systemic hypotension in infants is incompletely understood. OBJECTIVES: The aim of this study was to characterise the relationship between predicted sildenafil exposure and hypotension i ... Full text Link to item Cite

Population Pharmacokinetics of Trimethoprim-Sulfamethoxazole in Infants and Children.

Journal Article Antimicrob Agents Chemother · January 2018 Trimethoprim (TMP)-sulfamethoxazole (SMX) is used to treat various types of infections, including community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and Pneumocystis jirovecii infections in children. Pharmacokinetic (PK) data for infa ... Full text Link to item Cite

Development of an Adult Physiologically Based Pharmacokinetic Model of Solithromycin in Plasma and Epithelial Lining Fluid.

Journal Article CPT Pharmacometrics Syst Pharmacol · December 2017 Solithromycin is a fluoroketolide antibiotic under investigation for community-acquired bacterial pneumonia (CABP). We developed a whole-body physiologically based pharmacokinetic (PBPK) model for solithromycin in adults using PK-Sim and MoBi version 6.2, ... Full text Link to item Cite

External Evaluation of Two Fluconazole Infant Population Pharmacokinetic Models.

Journal Article Antimicrob Agents Chemother · December 2017 Fluconazole is an antifungal agent used for the treatment of invasive candidiasis, a leading cause of morbidity and mortality in premature infants. Population pharmacokinetic (PK) models of fluconazole in infants have been previously published by Wade et a ... Full text Link to item Cite

Development of a Pediatric Physiologically-Based Pharmacokinetic Model of Clindamycin Using Opportunistic Pharmacokinetic Data.

Journal Article Clin Pharmacokinet · November 2017 Physiologically-based pharmacokinetic (PBPK) modeling is a powerful tool used to characterize maturational changes in drug disposition to inform dosing across childhood; however, its use is limited in pediatric drug development. Access to pediatric pharmac ... Full text Link to item Cite

Population Pharmacokinetics/Pharmacodynamics of 3,4-Diaminopyridine Free Base in Patients With Lambert-Eaton Myasthenia.

Conference CPT Pharmacometrics Syst Pharmacol · September 2017 Lambert-Eaton myasthenia (LEM) is a rare autoimmune disorder associated with debilitating muscle weakness. There are limited treatment options and 3,4-diaminopyridine (3,4-DAP) free base is an investigational orphan drug used to treat LEM-related weakness. ... Full text Link to item Cite

Use of Population Pharmacokinetics and Electronic Health Records to Assess Piperacillin-Tazobactam Safety in Infants.

Journal Article Pediatr Infect Dis J · September 2017 BACKGROUND: Piperacillin, in combination with tazobactam, is frequently used in infants for treating nosocomial infections, although safety data in this population are limited. Electronic health record (EHR) data can be used to evaluate drug safety in infa ... Full text Link to item Cite

Methodological and Ethical Issues in Pediatric Medication Safety Research.

Journal Article Pediatrics · September 2017 In May 2016, the Eshelman School of Pharmacy at The University of North Carolina at Chapel Hill convened the PharmSci conference to address the topic of "methodological and ethical issues in pediatric medication safety research." A multidisciplinary group ... Full text Link to item Cite

Population Pharmacokinetics and Exploratory Pharmacodynamics of Lorazepam in Pediatric Status Epilepticus.

Journal Article Clin Pharmacokinet · August 2017 BACKGROUND: Lorazepam is one of the preferred agents used for intravenous treatment of status epilepticus (SE). We combined data from two pediatric clinical trials to characterize the population pharmacokinetics of intravenous lorazepam in infants and chil ... Full text Link to item Cite

Dalbavancin Pharmacokinetics and Safety in Children 3 Months to 11 Years of Age.

Journal Article Pediatr Infect Dis J · July 2017 BACKGROUND: Dalbavancin is a novel lipoglycopeptide antibiotic that has potent in vitro activity against Gram-positive microorganisms. METHODS: We performed a phase 1, open-label, multicenter study to investigate the pharmacokinetics (PK) and safety of a s ... Full text Link to item Cite

Population Pharmacokinetics of Morphine in Patients With Nonalcoholic Steatohepatitis (NASH) and Healthy Adults.

Journal Article CPT Pharmacometrics Syst Pharmacol · May 2017 Altered expression and function of transporters in nonalcoholic steatohepatitis (NASH) patients may affect the pharmacokinetics (PK), efficacy, and safety of substrate drugs. A population pharmacokinetic (PopPK) analysis was performed to assess differences ... Full text Link to item Cite

Pharmacokinetics of Clindamycin in Obese and Nonobese Children.

Journal Article Antimicrob Agents Chemother · April 2017 Although obesity is prevalent among children in the United States, pharmacokinetic (PK) data for obese children are limited. Clindamycin is a commonly used antibiotic that may require dose adjustment in obese children due to its lipophilic properties. We p ... Full text Link to item Cite

A Systematic Literature Review Approach to Estimate the Therapeutic Index of Selected Immunosuppressant Drugs After Renal Transplantation.

Journal Article Ther Drug Monit · February 2017 BACKGROUND: Drugs that exhibit close margins between therapeutic and toxic blood concentrations are considered to have a narrow therapeutic index (NTI). The Food and Drug Administration has proposed that NTI drugs should have more stringent bioequivalence ... Full text Link to item Cite

Clinical Pharmacology Studies in Critically Ill Children.

Journal Article Pharm Res · January 2017 Developmental and physiological changes in children contribute to variation in drug disposition with age. Additionally, critically ill children suffer from various life-threatening conditions that can lead to pathophysiological alterations that further aff ... Full text Link to item Cite

Use of Therapeutic Drug Monitoring, Electronic Health Record Data, and Pharmacokinetic Modeling to Determine the Therapeutic Index of Phenytoin and Lamotrigine.

Journal Article Ther Drug Monit · December 2016 BACKGROUND: Defining a drug's therapeutic index (TI) is important for patient safety and regulating the development of generic drugs. For many drugs, the TI is unknown. A systematic approach was developed to characterize the TI of a drug using therapeutic ... Full text Link to item Cite

Exposure Matching for Extrapolation of Efficacy in Pediatric Drug Development.

Journal Article J Clin Pharmacol · November 2016 During drug development, matching adult systemic exposures of drugs is a common approach for dose selection in pediatric patients when efficacy is partially or fully extrapolated. This is a systematic review of approaches used for matching adult systemic e ... Full text Link to item Cite

Therapeutic Drug Monitoring, Electronic Health Records, and Pharmacokinetic Modeling to Evaluate Sirolimus Drug Exposure-Response Relationships in Renal Transplant Patients.

Journal Article Ther Drug Monit · October 2016 BACKGROUND: Sirolimus, an immunosuppressive agent used in renal transplantation, can prevent allograft rejection. Identification of the therapeutic index (the ratio of minimum toxic concentration to minimum therapeutic concentration) for immunosuppresants ... Full text Link to item Cite

An opportunistic study evaluating pharmacokinetics of sildenafil for the treatment of pulmonary hypertension in infants.

Journal Article J Perinatol · September 2016 OBJECTIVE: The objective of this study is to assess sildenafil and N-desmethyl sildenafil (DMS) exposure in infants receiving sildenafil for the treatment of pulmonary hypertension (PH). STUDY DESIGN: Data were collected from six infants receiving sildenaf ... Full text Link to item Cite

Exposure Matching of Pediatric Anti-infective Drugs: Review of Drugs Submitted to the Food and Drug Administration for Pediatric Approval.

Journal Article Clin Ther · September 2016 PURPOSE: Over the last decade, few new antibiotics have been approved by the Food and Drug Administration (FDA) for pediatric use. For most anti-infective agents, including antibiotics, extrapolation of efficacy from adults to children is possible if the d ... Full text Link to item Cite

Pharmacokinetic and Pharmacodynamic Principles of Anti-infective Dosing.

Journal Article Clin Ther · September 2016 PURPOSE: An understanding of the pharmacokinetic (PK) and pharmacodynamic (PD) principles that determine response to antimicrobial therapy can provide the clinician with better-informed dosing regimens. Factors influential on antibiotic disposition and cli ... Full text Link to item Cite

Advances in Pediatric Pharmacology, Therapeutics, and Toxicology.

Journal Article Adv Pediatr · August 2016 In the United States, the Best Pharmaceuticals for Children Act and the Pediatric Research Equity Act continue to promote clinical trials in pediatric populations across all age ranges. In 2014 and 2015, over 70 changes were made to drug labels with update ... Full text Link to item Cite

Clindamycin Pharmacokinetics and Safety in Preterm and Term Infants.

Journal Article Antimicrob Agents Chemother · May 2016 Clindamycin may be active against methicillin-resistant Staphylococcus aureus, a common pathogen causing sepsis in infants, but optimal dosing in this population is unknown. We performed a multicenter, prospective pharmacokinetic (PK) and safety study of c ... Full text Link to item Cite

Solithromycin Pharmacokinetics in Plasma and Dried Blood Spots and Safety in Adolescents.

Journal Article Antimicrob Agents Chemother · April 2016 We assessed the pharmacokinetics and safety of solithromycin, a fluoroketolide antibiotic, in a phase 1, open-label, multicenter study of 13 adolescents with suspected or confirmed bacterial infections. On days 3 to 5, the mean (standard deviation) maximum ... Full text Link to item Cite

Pharmacokinetics and Dosing of Levofloxacin in Children Treated for Active or Latent Multidrug-resistant Tuberculosis, Federated States of Micronesia and Republic of the Marshall Islands.

Journal Article Pediatr Infect Dis J · April 2016 BACKGROUND: In the Federated States of Micronesia and then the Republic of the Marshall Islands (RMI), levofloxacin pharmacokinetics were studied in children receiving directly observed once-daily regimens (10 mg/kg, age >5 years; 15-20 mg/kg, age ≤5 years ... Full text Link to item Cite

Therapeutic Index Estimation of Antiepileptic Drugs: A Systematic Literature Review Approach.

Journal Article Clin Neuropharmacol · 2016 OBJECTIVES: Our study aimed to determine whether data obtained from the medical literature can be used to estimate the therapeutic index of 5 antiepileptic drugs (AEDs): carbamazepine, lamotrigine, phenobarbital, phenytoin, and valproate. METHODS: We perfo ... Full text Link to item Cite

Pharmacologic studies in vulnerable populations: Using the pediatric experience.

Journal Article Semin Perinatol · November 2015 Historically, few data exist to guide dosing in children and pregnant women. Multiple barriers to inclusion of these vulnerable populations in clinical trials have led to this paucity of data. However, federal legislation targeted at pediatric therapeutics ... Full text Link to item Cite

Fluconazole population pharmacokinetics and dosing for prevention and treatment of invasive Candidiasis in children supported with extracorporeal membrane oxygenation.

Journal Article Antimicrob Agents Chemother · July 2015 Candida infections are a leading cause of infectious disease-related death in children supported by extracorporeal membrane oxygenation (ECMO). The ECMO circuit can alter drug pharmacokinetics (PK); thus, standard fluconazole dosing may result in suboptima ... Full text Link to item Cite

Drug Dosing and Pharmacokinetics in Children With Obesity: A Systematic Review.

Journal Article JAMA Pediatr · July 2015 IMPORTANCE: Obesity affects nearly one-sixth of US children and results in alterations to body composition and physiology that can affect drug disposition, possibly leading to therapeutic failure or toxic side effects. The depth of available literature reg ... Full text Link to item Cite

Lessons learned in pediatric clinical research to evaluate safe and effective use of drugs in pregnancy.

Journal Article Obstet Gynecol · April 2015 Children and pregnant women are vulnerable populations lacking clinical data to guide drug dosing. For children, over the past 15 years, the knowledge gap in pharmacokinetic, safety, and efficacy data has been narrowed as a result of the use of innovative ... Full text Link to item Cite

Simultaneous determination of trimethoprim and sulfamethoxazole in dried plasma and urine spots.

Journal Article Bioanalysis · 2015 BACKGROUND: Trimethoprim-sulfamethoxazole (TMP-SMX) is an antimicrobial drug combination commonly prescribed in children and adults. The study objectives were to validate and apply an HPLC-MS/MS method to quantify TMP-SMX in dried plasma spots (DPS) and dr ... Full text Link to item Cite

Vancomycin cerebrospinal fluid pharmacokinetics in children with cerebral ventricular shunt infections.

Journal Article Pediatr Infect Dis J · October 2014 This study described the cerebrospinal fluid (CSF) exposure of vancomycin in 8 children prescribed intravenous vancomycin therapy for cerebral ventricular shunt infection. Vancomycin CSF concentrations ranged from 0.06 to 9.13 mg/L and the CSF: plasma rati ... Full text Link to item Cite

Use of opportunistic clinical data and a population pharmacokinetic model to support dosing of clindamycin for premature infants to adolescents.

Journal Article Clin Pharmacol Ther · October 2014 Clindamycin is commonly prescribed to treat children with skin and skin-structure infections (including those caused by community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA)), yet little is known about its pharmacokinetics (PK) across pe ... Full text Link to item Cite

Advances in pediatric pharmacology, therapeutics, and toxicology.

Journal Article Adv Pediatr · August 2014 In the United States, passage of the FDASIA legislation made BPCA and PREA permanent, no longer requiring reauthorization every 5 years. This landmark legislation also stressed the importance of performing clinical trials in neonates when appropriate. In E ... Full text Link to item Cite

Pharmacokinetics and safety of recently approved drugs used to treat methicillin-resistant Staphylococcus aureus infections in infants, children and adults.

Journal Article Expert Rev Clin Pharmacol · May 2014 Methicillin-resistant Staphylococcus aureus (MRSA) remains a significant cause of morbidity in hospitalized infants. Over the past 15 years, several drugs have been approved for the treatment of S. aureus infections in adults (linezolid, quinupristin/dalfo ... Full text Link to item Cite

Thromboprophylaxis with fondaparinux in high-risk postoperative patients with renal insufficiency.

Journal Article Thromb Res · April 2014 Fondaparinux is an antithrombin-dependent factor Xa inhibitor that is used for thromboprophylaxis of patients undergoing hip fracture surgery, hip or knee replacement, or abdominal surgery. It is cleared by the kidney and should be used with caution in pat ... Full text Link to item Cite

Relevance of Liver Failure for Anti-Infective Agents: From Pharmacokinetic Alterations to Dosage Adjustments.

Journal Article Ther Adv Infect Dis · February 1, 2014 The liver is a complex organ with great ability to influence drug pharmacokinetics. Due to its wide array of function, its impairment has the potential to affect bioavailability, enterohepatic circulation, drug distribution, metabolism, clearance, and bili ... Full text Link to item Cite

Comparison of skin permeability for three diclofenac topical formulations: an in vitro study.

Journal Article Pharmazie · January 2014 Diclofenac is a hydrophilic non-steroidal anti-inflammatory drug (NSAID) widely used in humans and animals. There are limited published studies evaluating diclofenac's skin permeation following topical administration. The aim of our study was to evaluate a ... Link to item Cite

A novel breath test to directly measure use of vaginal gel and condoms.

Journal Article AIDS Behav · July 2013 We assessed the feasibility of a breath test to detect women's single or concurrent use of vaginal products by adding ester taggants to vaginal gel and condom lubricant. Healthy non-pregnant women were enrolled into a two-day cohort (N = 13) and a single-d ... Full text Link to item Cite

Importance of relating efficacy measures to unbound drug concentrations for anti-infective agents.

Journal Article Clin Microbiol Rev · April 2013 For the optimization of dosing regimens of anti-infective agents, it is imperative to have a good understanding of pharmacokinetics (PK) and pharmacodynamics (PD). Whenever possible, drug efficacy needs to be related to unbound concentrations at the site o ... Full text Link to item Cite

Oral adherence monitoring using a breath test to supplement highly active antiretroviral therapy.

Journal Article AIDS Behav · January 2013 A breath-based adherence system to document ingestion of oral medications (e.g., HAART) was investigated. Specifically, the food additive 2-butanol, which can be easily packaged with a drug, is converted via alcohol dehydrogenase to the volatile metabolite ... Full text Link to item Cite

Feasibility of a breath test for monitoring adherence to vaginal administration of antiretroviral microbicide gels.

Journal Article J Clin Pharmacol · January 2013 Adherence to microbicide gel use is critical to optimizing effectiveness in preventing human immunodeficiency virus transmission. The authors hypothesized that ester taggants added to vaginal gels would generate exhaled alcohol and ketone metabolites and p ... Full text Link to item Cite

The effect of critical illness on drug distribution.

Journal Article Curr Pharm Biotechnol · December 2011 The complexity of managing critically ill patients has increased since the early establishment of intensive care units in the 1950s. Despite of the fact that the number of drugs available to clinicians has increased, the understanding of the pharmacokineti ... Full text Link to item Cite

Role of drug absorption in the pharmacokinetics of therapeutic interventions for stroke.

Journal Article Ann N Y Acad Sci · October 2010 Absorption is a critical component of the pharmacokinetics for solid dosage forms administered orally. Many barriers must be overcome in order for a drug molecule to reach its effect site. To effectively address each of these barriers, drug-specific proper ... Full text Link to item Cite

Significance of protein binding in pharmacokinetics and pharmacodynamics.

Journal Article J Pharm Sci · March 2010 The significance of plasma protein binding on drug efficacy and, subsequently, the clinical relevance of changes in protein binding has been controversially discussed for decades. The uncertainty concerning the impact of plasma protein binding on a drug's ... Full text Link to item Cite