Time-dependent inhibition of CYP3A4-mediated midazolam metabolism by macrolide antibiotics in CYP3A4 genetic variants: Comparison with testosterone metabolism.

ABSTRACT:

Objectives

The present study aimed to evaluate the effects of CYP3A4 genetic variation on the kinetics of mechanism-based inhibition (MBI) of both inhibitors using midazolam as a substrate for comparison with our previous study, as midazolam and testosterone have different binding sites.

Background

The genetic variation of cytochrome P450 (CYP) 3A4 affects MBI, expressed as the maximum inactivation rate constant (k_inact,max) and the inhibitor concentration required to achieve half-maximal inactivation (K_I). We previously showed, using testosterone as a substrate, that the MBI kinetics of erythromycin and clarithromycin differ among CYP3A4 variants.

Materials and methods

Midazolam 1'-hydroxylation inactivation profiles of erythromyci

SUBMITTER: Akiyoshi T 

PROVIDER: S-EPMC8795987 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature