Open AccessA Retrospective Evaluation of Allometry, Population Pharmacokinetics, and Physiologically‐Based Pharmacokinetics for Pediatric Dosing Using Clearance as a Surrogate
Author(s) -
Wu Qier,
Peters Sheila Annie
Publication year - 2019
Publication title -
cpt: pharmacometrics and systems pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.53
H-Index - 37
ISSN - 2163-8306
DOI - 10.1002/psp4.12385
Subject(s) - pharmacokinetics , extrapolation , population , medicine , dosing , range (aeronautics) , allometry , pharmacology , biology , statistics , mathematics , ecology , environmental health , materials science , composite material
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.