Application of Physiologically-Based and Population Pharmacokinetic Modeling for Dose Finding and Confirmation During the Pediatric Development of Moxifloxacin.
Journal
CPT: pharmacometrics & systems pharmacology
ISSN: 2163-8306
Titre abrégé: CPT Pharmacometrics Syst Pharmacol
Pays: United States
ID NLM: 101580011
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
12
02
2019
accepted:
15
05
2019
pubmed:
17
7
2019
medline:
20
8
2020
entrez:
17
7
2019
Statut:
ppublish
Résumé
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 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.
Identifiants
pubmed: 31310051
doi: 10.1002/psp4.12446
pmc: PMC6765696
doi:
Substances chimiques
Anti-Bacterial Agents
0
Moxifloxacin
U188XYD42P
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
654-663Informations de copyright
© 2019 Bayer AG, Leverkusen Germany CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of the American Society for Clinical Pharmacology and Therapeutics.
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