title: Persistent pharmacokinetic challenges to pediatric drug development.
abstract: The development of new therapeutic agents for the mitigation of pediatric disorders is largely hindered by the inability for investigators to assess pediatric pharmacokinetics (PK) in healthy patients due to substantial safety concerns. Pediatric patients are a clinical moving target for drug delivery due to changes in absorption, distribution, metabolism and excretion (ADME) and the potential for PK related toxicological (T) events to occur throughout development. These changes in ADMET can have profound effects on drug delivery, and may lead to toxic or sub-therapeutic outcomes. Ethical, economical, logistical, and technical barriers have resulted in insufficient investigation of these changes by industrial, regulatory, and academic bodies, leading to the classification of pediatric patients as therapeutic orphans. In response to these concerns, regulatory agencies have incentivized investigation into these ontogenic changes and their effects on drug delivery in pediatric populations. The intent of this review is to briefly present a synopsis of the development changes that occur in pediatric patients, discuss the effects of these changes on ADME and drug delivery strategies, highlight the hurdles that are still being faced, and present some opportunities to overcome these challenges.
authors.affiliation: Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University West Lafayette, IN, USA.
authors.forename: Daniel P
authors.initials: DP
authors.lastname: Sage
authors.affiliation: Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University West Lafayette, IN, USA.
authors.forename: Christopher
authors.initials: C
authors.lastname: Kulczar
authors.affiliation: Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University West Lafayette, IN, USA.
authors.forename: Wyatt
authors.initials: W
authors.lastname: Roth
authors.affiliation: Department of Medicinal Chemistry and Molecular Pharmacology, College of Pharmacy, Purdue University West Lafayette, IN, USA.
authors.forename: Wanqing
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Industrial and Physical Pharmacy, College of Pharmacy, Purdue University West Lafayette, IN, USA.
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Knipp
keywords: ADME; PBPK; ontogeny; pediatric; pharmacokinetic