A Physiologically Based Pharmacokinetic Model to Predict Determinants of Variability in Epirubicin Exposure and Tissue Distribution.

ABSTRACT:

Background

Epirubicin is an anthracycline antineoplastic drug that is primarily used in combination therapies for the treatment of breast, gastric, lung and ovarian cancers and lymphomas. Epirubicin is administered intravenously (IV) over 3 to 5 min once every 21 days with dosing based on body surface area (BSA; mg/m²). Despite accounting for BSA, marked inter-subject variability in circulating epirubicin plasma concentration has been reported.

Methods

In vitro experiments were conducted to determine the kinetics of epirubicin glucuronidation by human liver microsomes in the presence and absence of validated UGT2B7 inhibitors. A full physiologically based pharmacokinetic model was built and validated using Simcyp^® (version 19.1, Certara, Princeton, NJ,

SUBMITTER: Ansaar R 

PROVIDER: S-EPMC10143085 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature