Physiologically based absorption modelling to predict the impact of drug properties on pharmacokinetics of bitopertin.

ABSTRACT: Bitopertin (RG1678) is a glycine reuptake inhibitor in phase 3 trials for treatment of schizophrenia. Its clinical oral pharmacokinetics is sensitive to changes in drug substance particle size and dosage form. Physiologically based pharmacokinetic (PBPK) absorption model simulations of the impact of changes in particle size and dosage form (either capsules, tablets, or an aqueous suspension) on oral pharmacokinetics was verified by comparison to measured plasma concentrations. Then, a model parameter sensitivity analysis was applied to set limits on the particle sizes included in tablets for the market. The model was also used to explore the in vitro to in vivo correlation. Simulated changes in oral pharmacokinetics caused by differences in particle size and dosage form were confirmed in t

SUBMITTER: Parrott N 

PROVIDER: S-EPMC4147056 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature