title: A Survey of Neonatal Pharmacokinetic and Pharmacodynamic Studies in Pediatric Drug Development.
abstract: Conducting clinical trials in neonates is challenging, and knowledge gaps in neonatal clinical pharmacology exist. We surveyed the US Food and Drug Administration databases and identified 43 drugs studied in neonates or referring to neonates between 1998 and 2014. Twenty drugs were approved in neonates. For 10 drugs, approval was based on efficacy data in neonates, supplemented by pharmacokinetic data for four drugs. Approval for neonates was based on full extrapolation from older patients for six drugs, and partial extrapolation was the basis of approval for four drugs. Dosing recommendations differed from older patients for most drugs, and used body-size based adjustment in neonates. Trial failures were associated with various factors including inappropriate dose selection. Successful drug development in neonates could be facilitated by an improved understanding of the natural history and pathophysiology of neonatal diseases and identification and validation of clinically relevant biomarkers.
authors.affiliation: Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Office of Pediatric Therapeutics, Commissioner's Office, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: D
authors.initials: D
authors.lastname: Avant
authors.affiliation: Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: D
authors.initials: D
authors.lastname: Green
authors.affiliation: Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: S
authors.initials: S
authors.lastname: Seo
authors.affiliation: Division of Biochemical Toxicology, National Center for Toxicology Research, U.S. Food and Drug Administration, Jefferson, Arkansas, USA.
authors.forename: J
authors.initials: J
authors.lastname: Fisher
authors.affiliation: Division of Gastroenterology and Inborn Errors Products, Office of Drug Evaluation III, Center for Drug Evaluation and Research, Silver Spring, Maryland, USA, U.S. Food and Drug Administration.
authors.forename: A E
authors.initials: AE
authors.lastname: Mulberg
authors.affiliation: Office of Translational Sciences, Center for Drug Evaluation and Research U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: S K
authors.initials: SK
authors.lastname: McCune
authors.affiliation: Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
authors.forename: G J
authors.initials: GJ
authors.lastname: Burckart
mesh_terms: D000367:Age Factors; D000465:Algorithms; D002986:Clinical Trials as Topic; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D054796:Drug Dosage Calculations; D064420:Drug-Related Side Effects and Adverse Reactions / Q000209:etiology / Q000517:prevention & control; D006801:Humans; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000008:administration & dosage* / Q000378:metabolism; D010599:Pharmacokinetics; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D004364:Pharmaceutical Preparations