Pregnancy related hormones increase CYP3A mediated buprenorphine metabolism in human hepatocytes: a comparison to CYP3A substrates nifedipine and midazolam.

ABSTRACT: Introduction: Pregnancy increases the clearance of CYP3A4 substrate drugs and pregnancy-related hormones (PRHs) induce hepatic CYP3A4 expression and metabolism. However, it remains unclear to what extent the magnitude of PRH-evoked changes in hepatic CYP3A metabolism varies across multiple substrates. This study quantified the impact of PRHs on CYP3A protein concentrations and buprenorphine metabolism in human hepatocytes, and compared the magnitude of these effects to nifedipine and midazolam metabolism. Methods: Sandwich-cultured human hepatocytes (SCHH) from female donors were exposed to PRHs, administered in combination across a range of physiologically relevant concentrations, for 72 h. Absolute protein concentrations of CYP3A4, CYP3A5, and CYP3A7 in SCHH membrane fracti

SUBMITTER: Fashe MM 

PROVIDER: S-EPMC10354249 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature