Prediction of Clinical Transporter-Mediated Drug-Drug Interactions via Comeasurement of Pitavastatin and Eltrombopag in Human Hepatocyte Models.

ABSTRACT: A structurally identifiable micro-rate constant mechanistic model was used to describe the interaction between pitavastatin and eltrombopag, with improved goodness-of-fit values through comeasurement of pitavastatin and eltrombopag. Transporter association and dissociation rate constants and passive rates out of the cell were similar between pitavastatin and eltrombopag. Translocation into the cell through transporter-mediated uptake was six times greater for pitavastatin, leading to pronounced inhibition of pitavastatin uptake by eltrombopag. The passive rate into the cell was 91 times smaller for pitavastatin compared with eltrombopag. A semimechanistic physiologically-based pharmacokinetic (PBPK) model was developed to evaluate the potential for clinical drug-drug interactions (DDIs). T

SUBMITTER: Carter SJ 

PROVIDER: S-EPMC7179958 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature