Increased coproporphyrin serum levels in healthy volunteers treated with the cholesterol uptake inhibitor ezetimibe.

ABSTRACT: Ezetimibe undergoes glucuronidation that results in the active metabolite ezetimibe phenoxy-glucuronide (ezetimibe-glucuronide). This phase-II metabolite was shown to interact with the clinically relevant hepatic transporter organic anion transporting polypeptide (OATP) 1B1. In recent years, coproporphyrin I (CPI) was established as a Tier 1 biomarker for OATP1B-mediated interactions among other endogenous substrates like CPIII. To evaluate whether levels of the biomarker are affected by ezetimibe treatment, we assessed the impact of ezetimibe and ezetimibe-glucuronide on OATP1B1-mediated transport of CPs in vitro. Then, we quantified CP levels in serum samples of healthy volunteers treated with a single oral dose of ezetimibe (20 mg) alone or in combination with rifampin (600 mg). Results

SUBMITTER: Kinzi J 

PROVIDER: S-EPMC11476718 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature