A Retrospective Evaluation of Allometry, Population Pharmacokinetics, and Physiologically‐Based Pharmacokinetics for Pediatric Dosing Using Clearance as a Surrogate

• Published in: CPT: pharmacometrics and systems pharmacology Vol. 8; no. 4; pp. 220 - 229
• Main Authors: Wu, Qier, Peters, Sheila Annie
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01-04-2019; John Wiley and Sons Inc
• Subjects: Adults; Age; Corporate sponsorship; Drug dosages; Equity; FDA approval; Knowledge; Pediatrics; Pharmacokinetics; Physiology; Population; Regulatory agencies; Studies; United States > US
• ISSN: 2163-8306; 2163-8306
• DOI: 10.1002/psp4.12385

Physiologically‐based pharmacokinetic models are increasingly applied for pediatric dose selection along with traditional methods such as allometry and population pharmacokinetic models. We report a retrospective evaluation of the three methods. Pediatric population pharmacokinetic models sourced from literature for a subset of eight compounds were used to predict clearances for children < 2 years when they were within the modeled age range (interpolation, N = 11) or including those outside the modeled age range (interpolation and extrapolation, N = 18). Pediatric/adult clearance ratios were evaluated with a strict performance criterion of 0.8–1.25 and with twofold criteria. For children > 2 years, 58–75% of the clinical studies (N = 10) met the strict criteria, and > 80% of the clinical studies were predicted within twofold by all three methods. For children < 2 years, physiologically‐based pharmacokinetic, allometry with age‐dependent exponents, and pediatric population pharmacokinetic models predict 54%, 82%, and 64% within twofold of the observed, respectively.