Comparison between physiologically based pharmacokinetic and population pharmacokinetic modelling to select paediatric doses of gepotidacin in plague.

ABSTRACT:

Aims

To develop physiologically based pharmacokinetic (PBPK) and population pharmacokinetic (PopPK) models to predict effective doses of gepotidacin in paediatrics for the treatment of pneumonic plague (Yersinia pestis).

Methods

A gepotidacin PBPK model was constructed using a population-based absorption, distribution, metabolism and excretion simulator, Simcyp®, with physicochemical and in vitro data, optimized with clinical data from a dose-escalation intravenous (IV) study and a human mass balance study. A PopPK model was developed with pooled PK data from phase 1 studies with IV gepotidacin in healthy adults.

Results

For both the PopPK and PBPK models, body weight was found to be a key covariate affecting gepotidacin clearance. With PBPK, ~90% of the predicted PK

SUBMITTER: Nguyen D 

PROVIDER: S-EPMC9293063 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature