Scholars@Duke
Chi Hornik

Chi Hornik

Associate Professor of Pediatrics
Pediatrics, Critical Care Medicine
2301 Erwin Road, 5th Floor Duke North, Suite 5260Y, Durham, NC 27710
DUMC, 2301 Erwin Road, 5th Floor Duke North, Suite 5260Y, Durham, NC 27710

Selected Publications

Pharmacokinetics of Dexamethasone in Children and Adolescents with Obesity.

Journal Article J Clin Pharmacol · December 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

Epidemiology and treatment of herpes simplex virus in the neonatal intensive care unit.

Journal Article J Perinatol · October 11, 2024 OBJECTIVE: Describe the epidemiology and clinical characteristics of infants in the neonatal intensive care unit (NICU) with acyclovir exposure and herpes simplex virus (HSV) infection. STUDY DESIGN: Our primary analysis was to evaluate the prevalence of H ... Full text Link to item Cite

Postdiscontinuation Antibiotic Exposure in Hospitalized Infants at Risk for Late-onset Sepsis in the Neonatal Intensive Care Unit.

Journal Article Pediatr Infect Dis J · October 1, 2024 BACKGROUND: In the neonatal intensive care unit, infants are at risk for late-onset sepsis. When blood cultures are negative, antibiotic stewardship efforts encourage stopping antibiotics, yet the duration of therapeutic exposure after the last dose is unk ... Full text Link to item Cite

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

Journal Article J Clin Pharmacol · 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 Link to item 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

Decreasing Blood Transfusions in Premature Infants Through Quality Improvement.

Journal Article Pediatrics · August 1, 2024 BACKGROUND AND OBJECTIVES: Packed red blood cell transfusions (pRBCT) in preterm infants have been associated with significant morbidity. Although infants <26 weeks' gestational age typically require several pRBCT, preterm infants born between 26 and 34 we ... Full text Link to item Cite

The severity of MUSK pathogenic variants is predicted by the protein domain they disrupt.

Journal Article HGG Adv · July 18, 2024 Biallelic loss-of-function variants in the MUSK gene result in two allelic disorders: (1) congenital myasthenic syndrome (CMS; OMIM: 616325), a neuromuscular disorder that has a range of severity from severe neonatal-onset weakness to mild adult-onset weak ... 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

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 Clinical pharmacokinetics · June 2024 BackgroundLevetiracetam 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 ... Full text Cite

Insulin for Treatment of Neonatal Hyperglycemia in Premature Infants: Prevalence over Time and Association with Outcomes.

Journal Article Am J Perinatol · May 2024 OBJECTIVE: Our objective was to determine the prevalence of insulin treatment in premature infants with hyperglycemia and evaluate the association of length of treatment with outcomes. STUDY DESIGN: The study included cohort of 29,974 infants 22 to 32 week ... Full text Link to item Cite

Opportunistic dried blood spot sampling validates and optimizes a pediatric population pharmacokinetic model of metronidazole.

Journal Article Antimicrob Agents Chemother · April 3, 2024 Pharmacokinetic models rarely undergo external validation in vulnerable populations such as critically ill infants, thereby limiting the accuracy, efficacy, and safety of model-informed dosing in real-world settings. Here, we describe an opportunistic appr ... 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

An Overview of Data Management in Human Subjects Research.

Journal Article Respir Care · January 24, 2024 Research studies generate data in various forms. Data can be quantitative or qualitative. Research involving human subjects requires protection of data to ensure privacy. Various regulations and local policies need to be followed to ensure data security. D ... Full text Link to item Cite

Pharmacokinetics in Neonatal Medicine

Chapter · January 1, 2024 The safe and effective use of medications in the neonatal intensive care unit (NICU) requires an understanding of the principles of pharmacokinetics (PK) and pharmacodynamics (PD) that guide individual dosing and aim to provide drug exposures designed for ... Full text Cite

Change to Mixed-Lipid Emulsion From Soybean Oil-Based Lipid Emulsion in Pediatric Patients.

Journal Article JAMA Netw Open · September 5, 2023 IMPORTANCE: Critically ill pediatric patients often require parenteral nutrition (PN) in the intensive care unit (ICU). Literature suggests mixed lipid emulsions (LE) with soybean oil reduction strategies may improve outcomes. OBJECTIVE: To examine the ass ... Full text Open Access Link to item Cite

Dexmedetomidine Opioid Sparing Effect in Mechanically Ventilated Children (DOSE): Trial of Fentanyl versus Fentanyl + Dexmedetomidine for Maintenance of Sedation

Journal Article Journal of Pediatric Intensive Care · May 26, 2023 Abstract Objectives This article observes the mean daily dose of fentanyl required for adequate sedation in critically ill, mechanically ventilated children randomized to receive dexmedetomidine or placebo. Full text Cite

Mechanisms to expedite pediatric clinical trial site activation: The DOSE trial experience.

Journal Article Contemp Clin Trials · February 2023 BACKGROUND: Timely trial start-up is a key determinant of trial success; however, delays during start-up are common and costly. Moreover, data on start-up metrics in pediatric clinical trials are sparse. To expedite trial start-up, the Trial Innovation Net ... Full text Link to item Cite

Pharmacokinetics and Proposed Dosing of Levetiracetam in Children With Obesity.

Journal Article J Pediatr Pharmacol Ther · 2023 OBJECTIVE: Characterize levetiracetam pharmacokinetics (PK) in children with obesity to inform dosing. METHODS: Children 2 to <21 years old receiving standard of care oral levetiracetam across two opportunistic studies provided blood samples. Levetiracetam ... Full text Link to item Cite

Safety of sildenafil in premature infants at risk of bronchopulmonary dysplasia: Rationale and methods of a phase II randomized trial.

Journal Article Contemp Clin Trials Commun · December 2022 Bronchopulmonary dysplasia (BPD) is a disease of chronic respiratory insufficiency stemming from premature birth and iatrogenic lung injury leading to alveolar simplification, impaired alveolar-capillary development, interstitial fibrosis, and often pulmon ... Full text Link to item Cite

Safety and Pharmacokinetics of Exebacase in an Infant With Disseminated Staphylococcus aureus Infection.

Journal Article Clin Infect Dis · August 25, 2022 Exebacase, an antistaphylococcal lysin produced from a bacteriophage-encoded gene, is a promising adjunctive therapy for severe methicillin-resistant Staphylococcus aureus infections. We describe the first infant to receive exebacase, dosing, and pharmacok ... Full text Open Access 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

Solithromycin in Children and Adolescents With Community-acquired Bacterial Pneumonia.

Journal Article Pediatr Infect Dis J · July 1, 2022 BACKGROUND: Solithromycin is a new macrolide-ketolide antibiotic with potential effectiveness in pediatric community-acquired bacterial pneumonia (CABP). Our objective was to evaluate its safety and effectiveness in children with CABP. METHODS: This phase ... Full text Open Access 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

Severe Congenital Syphilis in the Neonatal Intensive Care Unit: A Retrospective Case Series.

Journal Article Pediatr Infect Dis J · April 1, 2022 BACKGROUND: There has been a 291% relative increase in congenital syphilis (CS) cases in the United States from 2015 to 2019. Although the majority of affected fetuses/infants are stillborn or are asymptomatic, a subset is born with severe clinical illness ... Full text Link to item 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

Medication Use in the Neonatal Intensive Care Unit and Changes from 2010 to 2018.

Journal Article J Pediatr · January 2022 OBJECTIVE: To provide up-to-date medication prescribing patterns in US neonatal intensive care units (NICUs) and to examine trends in prescribing patterns over time. STUDY DESIGN: We performed a cohort study of 799 016 infants treated in NICUs managed by t ... Full text Link to item Cite

Neonatal invasive candidiasis: updates on clinical management and prevention.

Journal Article Lancet Child Adolesc Health · January 2022 Neonatal invasive candidiasis is an important cause of morbidity and mortality in preterm infants. The incidence of invasive candidiasis in this population has been declining in high-income settings, largely due to preventive measures, although there are s ... Full text Link to item Cite

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

Journal Article Journal of perinatology : official journal of the California Perinatal Association · January 2022 ObjectiveTo characterize the safety of sildenafil in premature infants.Study designA 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 sil ... Full text 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 and Safety of Ceftobiprole in Pediatric Patients.

Journal Article Pediatr Infect Dis J · November 1, 2021 BACKGROUND: Ceftobiprole, the active moiety of the prodrug ceftobiprole medocaril, is an advanced-generation, broad-spectrum, intravenous cephalosporin, which is currently approved for the treatment of adults with hospital-acquired or community-acquired pn ... Full text Link to item Cite

Neuropalliative Care for Neonates.

Journal Article J Child Neurol · October 2021 Many childhood neurologic conditions are first diagnosed in the perinatal period and shorten or seriously alter the lives of affected infants. Neonatal neuropalliative care incorporates core practices and teachings of both neurology and palliative care and ... Full text Link to item Cite

Pharmacokinetics of Ceftazidime in Children and Adolescents with Obesity.

Journal Article Paediatr Drugs · September 2021 PURPOSE: The aim of this study was to evaluate ceftazidime pharmacokinetics (PK) in a cohort that includes a predominate number of children and adolescents with obesity and assess the efficacy of competing dosing strategies. METHODS: A population PK model ... Full text Link to item Cite

Association between neonatal intensive care unit medication safety practices, adverse events, and death.

Journal Article J Perinatol · July 2021 OBJECTIVE: Determine the associations between neonatal intensive care unit (NICU) medication safety practices, laboratory-based adverse events (lab-AEs), and death. STUDY DESIGN: We combined data from a 2016 survey of Pediatrix NICUs on use of medication s ... Full text Link to item Cite

Prolonged Post-Discontinuation Antibiotic Exposure in Very Low Birth Weight Neonates at Risk for Early-Onset Sepsis.

Journal Article J Pediatric Infect Dis Soc · May 28, 2021 BACKGROUND: Premature, very low birth weight (VLBW) neonates are at risk for early-onset sepsis and receive ampicillin and gentamicin post-birth. Antimicrobial stewardship supports short-course antibiotics, but how long antibiotic concentrations remain the ... Full text Link to item Cite

Racial and Ethnic Diversity in Studies Funded Under the Best Pharmaceuticals for Children Act.

Journal Article Pediatrics · May 2021 BACKGROUND AND OBJECTIVES: The Best Pharmaceuticals for Children Act (BPCA) incentivizes the study of on-patent medicines in children and mandates that the National Institutes of Health sponsor research on off-patent drugs important to pediatric therapeuti ... Full text Link to item Cite

Pharmacokinetics of Hydrochlorothiazide in Children: A Potential Surrogate for Renal Secretion Maturation.

Journal Article J Clin Pharmacol · March 2021 Hydrochlorothiazide (HCTZ) is a thiazide diuretic used in adults and children for the treatment of hypertension and edema. The pharmacokinetic (PK) properties of HCTZ in children are not well characterized, particularly among children with obesity who freq ... 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

Postnatally acquired CMV meningitis diagnosed via BioFire FilmArray: A case report.

Journal Article J Neonatal Perinatal Med · 2021 Postnatally acquired cytomegalovirus (CMV) is commonly acquired via breast milk, with premature infants more frequently developing symptoms of CMV infection in comparison to term infants. Meningitis is a rare clinical manifestation of CMV infection. The di ... Full text Link to item Cite

Review of Fluconazole Treatment and Prophylaxis for Invasive Candidiasis in Neonates.

Journal Article J Pediatr Pharmacol Ther · 2021 Invasive candidiasis accounts for approximately 10% of nosocomial infections in preterm infants, with an incidence of 1% to 4% among neonatal intensive care unit (NICU) admissions and a mortality as high as 20% to 30%. These outcomes warrant improved treat ... 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

Pharmacokinetic, efficacy, and safety considerations for the use of antifungal drugs in the neonatal population.

Journal Article Expert Opin Drug Metab Toxicol · July 2020 INTRODUCTION: Invasive fungal infections are an important cause of morbidity and mortality in infants, particularly in extreme prematurity. Successful systemic treatment requires consideration of antifungal efficacy, safety, and pharmacokinetics, including ... Full text Link to item Cite

Impact of Personal Protective Equipment on Pediatric Cardiopulmonary Resuscitation Performance: A Controlled Trial.

Journal Article Pediatr Emerg Care · June 2020 OBJECTIVES: This study aimed to determine whether personal protective equipment (PPE) results in deterioration in chest compression (CC) quality and greater fatigue for administering health care providers (HCPs). METHODS: In this multicenter study, HCPs co ... 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

Intranasal midazolam and fentanyl for procedural sedation and analgesia in infants in the neonatal intensive care unit.

Journal Article J Neonatal Perinatal Med · 2019 BACKGROUND: The intranasal route is a minimally invasive method for rapidly delivering midazolam and fentanyl to provide short-term analgesia and sedation in infants. However, intranasal use of midazolam and fentanyl is not labeled for infants and safety d ... Full text Link to item Cite

Antibiotic Dosing Considerations for Term and Preterm Infants

Chapter · January 1, 2018 Early and appropriate antibiotic therapy can be lifesaving for severe infections in infants. However, physiologic differences in infants compared with older children and adults contribute to challenges in neonatal dosing. Neonatal-specific dosing regimens ... Full text Cite

The role of oxidative stress, inflammation and acetaminophen exposure from birth to early childhood in the induction of autism.

Journal Article J Int Med Res · April 2017 The wide range of factors associated with the induction of autism is invariably linked with either inflammation or oxidative stress, and sometimes both. The use of acetaminophen in babies and young children may be much more strongly associated with autism ... Full text Link to item Cite

A case of infant delirium in the neonatal intensive care unit.

Journal Article J Neonatal Perinatal Med · 2017 Infant delirium is an under-recognized clinical entity in neonatal intensive care, and earlier identification and treatment could minimize morbidities associated with this condition. We describe a case of a 6-month-old former 32 weeks gestation infant unde ... Full text Link to item Cite

Gabapentin Use in the Neonatal Intensive Care Unit.

Journal Article J Pediatr · February 2016 Gabapentin was used for the treatment of term and preterm infants with suspected visceral hyperalgesia caused by a variety of neurologic and gastrointestinal morbidities. Improved feeding tolerance and decreased irritability were seen, as well as decreased ... Full text Link to item Cite

Pulmonary artery thrombus in a premature neonate treated with recombinant tissue plasminogen activator.

Journal Article J Perinatol · July 2014 Pulmonary artery thrombus is a rarely reported complication in premature neonates. The management of life-threatening thrombotic events in neonates is controversial, especially regarding the use of thrombolytics versus anticoagulation alone for treatment. ... Full text Link to item Cite

Ethical Considerations in Pharmacogenomic Testing and Research in Pediatrics

Chapter · May 6, 2014 It is critical to resolve ethical issues surrounding genome-based testing in children because of the growing availability of pharmacogenomic (PGx) testing, the establishment of pediatric DNA research databases, and the unforeseen future implications of ide ... Full text Cite

Effects of low-dose dopamine on urine output in normotensive very low birth weight neonates.

Journal Article J Perinatol · August 2013 OBJECTIVE: To determine the effects of low-dose dopamine on urine output (UOP) in very low birth weight premature neonates. STUDY DESIGN: Retrospective cohort study of all low-dose (3-5 μg kg(-1) per min) dopamine infusions >24-h duration in neonates 1500 ... Full text Link to item Cite

Recombinant activated factor VIIa treatment for refractory hemorrhage in infants.

Journal Article J Perinatol · March 2011 OBJECTIVE: Report clinical response to recombinant factor VIIa in a cohort of critically ill infants. STUDY DESIGN: We identified all infants who received factor VIIa in the Duke Neonatal Intensive Care Unit between January 2005 and July 2008. Hematologica ... Full text Link to item Cite

Vasopressin for refractory hypotension in extremely low birth weight infants.

Journal Article J Pediatr · September 2010 Intravenous vasopressin at 0.01 to 0.04 units/kg/h increased median mean blood pressure from 26 mm Hg (range 18-44) to 41 mm Hg (range 17-90) by 12 hours of infusion (P=.002) and allowed weaning of catecholamines in a group of extremely low birth weight in ... Full text Link to item Cite

Safety and effectiveness of indomethacin versus ibuprofen for treatment of patent ductus arteriosus.

Journal Article Am J Perinatol · May 2010 We compared the rates of medical closure of patent ductus arteriosus (PDA) and complications (renal dysfunction, necrotizing enterocolitis, spontaneous intestinal perforation, and intraventricular hemorrhage) between infants treated with indomethacin and i ... Full text Link to item Cite