A Retrospective Evaluation of Allometry, Population Pharmacokinetics, and Physiologically‐Based Pharmacokinetics for Pediatric Dosing Using Clearance as a Surrogate. (26th February 2019)

• Record Type: Journal Article
• Authors: Wu, Qier; Peters, Sheila Annie
• Is Part Of: CPT: pharmacometrics & systems pharmacology. Volume 8:Number 4(2019)
• Page Start: 220
• Page End: 229
• Publication Date: 2019-02-26
• Subjects: Pharmacokinetics -- Periodicals; Pharmacology -- Periodicals; Pharmacokinetics; Periodicals; 615.05
• DOI: 10.1002/psp4.12385
• Languages: English
• ISSNs: 2163-8306

Abstract

Abstract : 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.