A Survey of Neonatal Pharmacokinetic and Pharmacodynamic Studies in Pediatric Drug Development

J Wang; D Avant; D Green; S Seo; J Fisher; A E Mulberg; S K McCune; G J Burckart

doi:10.1002/cpt.149

A Survey of Neonatal Pharmacokinetic and Pharmacodynamic Studies in Pediatric Drug Development

Clin Pharmacol Ther. 2015 Sep;98(3):328-35. doi: 10.1002/cpt.149.

Authors

J Wang¹, D Avant², D Green¹, S Seo¹, J Fisher³, A E Mulberg⁴, S K McCune⁵, G J Burckart¹

Affiliations

¹ Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
² Office of Pediatric Therapeutics, Commissioner's Office, U.S. Food and Drug Administration, Silver Spring, Maryland, USA.
³ Division of Biochemical Toxicology, National Center for Toxicology Research, U.S. Food and Drug Administration, Jefferson, Arkansas, USA.
⁴ 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.
⁵ Office of Translational Sciences, Center for Drug Evaluation and Research U.S. Food and Drug Administration, Silver Spring, Maryland, USA.

PMID: 25975723
DOI: 10.1002/cpt.149

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.

Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Publication types

Review

MeSH terms

Age Factors
Algorithms
Clinical Trials as Topic*
Computer Simulation
Dose-Response Relationship, Drug
Drug Discovery*
Drug Dosage Calculations
Drug-Related Side Effects and Adverse Reactions / etiology
Drug-Related Side Effects and Adverse Reactions / prevention & control
Humans
Infant, Newborn
Infant, Newborn, Diseases / diagnosis
Infant, Newborn, Diseases / drug therapy*
Infant, Newborn, Diseases / metabolism
Models, Biological
Pharmaceutical Preparations / administration & dosage*
Pharmaceutical Preparations / metabolism
Pharmacokinetics*
Risk Assessment
Risk Factors

Substances

Pharmaceutical Preparations