Open AccessApplication of Physiologically‐Based and Population Pharmacokinetic Modeling for Dose Finding and Confirmation During the Pediatric Development of Moxifloxacin
Author(s) -
Willmann Stefan,
Frei Matthias,
Sutter Gabriele,
Coboeken Katrin,
Wendl Thomas,
Eissing Thomas,
Lippert Jörg,
Stass Heino
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/psp4.12446
Subject(s) - moxifloxacin , pharmacokinetics , pharmacology , physiologically based pharmacokinetic modelling , population pharmacokinetics , medicine , biology , antibiotics , microbiology and biotechnology
Moxifloxacin is a widely used fluoroquinolone for the treatment of complicated intra‐abdominal infections. We applied physiologically‐based pharmacokinetic ( PBPK ) and population pharmacokinetic (pop PK ) modeling to support dose selection in pediatric patients. We scaled an existing adult PBPK model to children based on prior physiological knowledge. The resulting model proposed an age‐dependent dosing regimen that was tested in a phase I study. Refined doses were then tested in a phase III study. A pop PK analysis of all clinical pediatric data confirmed the PBPK predictions, including the proposed dosing schedule in children, and supported pharmacokinetics ‐related safety/efficacy questions. The pediatric PBPK model adequately predicted the doses necessary to achieve antimicrobial efficacy while maintaining safety in the phase I and III pediatric studies. Altogether, this study retroactively demonstrated the robustness and utility of modeling to support dose finding and confirmation in pediatric drug development for moxifloxacin.