Evaluation of the drug-drug interaction potential of treosulfan using a physiologically-based pharmacokinetic modelling approach.

ABSTRACT:

Aims

The aim of this work is the development of a mechanistic physiologically-based pharmacokinetic (PBPK) model using in vitro to in vivo extrapolation to conduct a drug-drug interaction (DDI) assessment of treosulfan against two cytochrome p450 (CYP) isoenzymes and P-glycoprotein (P-gp) substrates.

Methods

A PBPK model for treosulfan was developed de novo based on literature and unpublished clinical data. The PBPK DDI analysis was conducted using the U.S. Food and Drug Administration (FDA) DDI index drugs (probe substrates) midazolam, omeprazole and digoxin for CYP3A4, CYP2C19 and P-gp, respectively. Qualified and documented PBPK models of the probe substrates have been adopted from an open-source online model database.

Results

The PBPK model for treosulfan, based o

SUBMITTER: Schaller S 

PROVIDER: S-EPMC9291915 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature