Quantitative Assessment of Elagolix Enzyme-Transporter Interplay and Drug-Drug Interactions Using Physiologically Based Pharmacokinetic Modeling.

ABSTRACT:

Introduction

Elagolix is approved for the management of moderate-to-severe pain associated with endometriosis. The aim of this analysis was to develop a physiologically based pharmacokinetic (PBPK) model that describes the enzyme-transporter interplay involved in the disposition of elagolix and to predict the magnitude of drug-drug interaction (DDI) potential of elagolix as an inhibitor of P-glycoprotein (P-gp) and inducer of cytochrome P450 (CYP) 3A4.

Methods

A PBPK model (SimCYP^® version 15.0.86.0) was developed using elagolix data from in vitro, clinical PK and DDI studies. Data from DDI studies were used to quantify contributions of the uptake transporter organic anion transporting polypeptide (OATP) 1B1 and CYP3A4 in the disposition of elagolix, and to quanti

SUBMITTER: Chiney MS 

PROVIDER: S-EPMC7217817 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature