Comprehensive PBPK model to predict drug interaction potential of Zanubrutinib as a victim or perpetrator.

ABSTRACT: A physiologically based pharmacokinetic (PBPK) model was developed to evaluate and predict (1) the effect of concomitant cytochrome P450 3A (CYP3A) inhibitors or inducers on the exposures of zanubrutinib, (2) the effect of zanubrutinib on the exposures of CYP3A4, CYP2C8, and CYP2B6 substrates, and (3) the impact of gastric pH changes on the pharmacokinetics of zanubrutinib. The model was developed based on physicochemical and in vitro parameters, as well as clinical data, including pharmacokinetic data in patients with B-cell malignancies and in healthy volunteers from two clinical drug-drug interaction (DDI) studies of zanubrutinib as a victim of CYP modulators (itraconazole, rifampicin) or a perpetrator (midazolam). This PBPK model was successfully validated to describe the observed plas

SUBMITTER: Wang K 

PROVIDER: S-EPMC8129716 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature