Application of Physiologically ‐Based and Population Pharmacokinetic Modeling for Dose Finding and Confirmation During the Pediatric Development of Moxifloxacin
Moxifloxacin is a widely used fluoroquinolone for the treatment of complicated intra ‐abdominal infections. We applied physiologically‐based pharmacokinetic (PBPK) and population pharmacokinetic (popPK) 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 popPK analysis of all clinical pediatric data confirmed the PBPK predictions, including the proposed dosing schedule in children, and supported pharmacokinetics‐related safe ty/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 findi ng and confirmation in pediatric drug development for moxifloxacin.
Source: CPT: Pharmacometrics and Systems Pharmacology - Category: Drugs & Pharmacology Authors: Stefan Willmann,
Matthias Frei,
Gabriele Sutter,
Katrin Coboeken,
Thomas Wendl,
Thomas Eissing,
J örg Lippert,
Heino Stass Tags: Article Source Type: research
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