Sex-Dependent Effects of CYP2D6 on the Pharmacokinetics of Berberine in Humans.

ABSTRACT: An over-the-counter product berberine (a major alkaloid in goldenseal) is a substrate of the uptake transporter OCT1 and the metabolizing enzyme CYP2D6. The two genes exhibit common functional polymorphisms. Approximately 9% of Europeans and white Americans are either poor CYP2D6 metabolizers or poor OCT1 transporters. In this study, we investigated the effects of OCT1 and CYP2D6 polymorphisms on berberine pharmacokinetics in humans. We confirmed in vitro that berberine is an OCT1 substrate (K_M of 7.0 μM, CL_int of 306 ± 29 μL/min/mg). Common OCT1 alleles *3 to *6 showed uptake reduced by at least 65% and Oct1/2 knockout mice showed 3.2-fold higher AUCs in liver perfusion experiments. However, in humans, poor OCT1 transporters did not show any differences in berberine

SUBMITTER: Blocher JA 

PROVIDER: S-EPMC11652804 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature