Bergamottin can be used to assess CYP3A-mediated intestinal first-pass metabolism without affecting P-glycoprotein-mediated efflux in rats.

Bergamottin can be used to assess CYP3A-mediated intestinal first-pass metabolism without affecting P-glycoprotein-mediated efflux in rats. Xenobiotica. 2019 Jul 18;:1-20 Authors: Suzuki K, Taniyama K, Aoyama T, Watanabe Y Abstract 1. We investigated whether bergamottin would be useful for evaluating CYP3A-mediated intestinal metabolism in rats utilising its characteristics as a mechanism-based inhibitor of CYP3A. 2. Buspirone and fexofenadine, probe substrates of CYP3A and P-glycoprotein (P-gp), respectively, were orally co-administered to rats with bergamottin (2.5 mg/kg) or orally administered 2 h after bergamottin pre-treatment. The effect of bergamottin pre-treatment on hepatic CYP3A specifically was investigated with intravenous administration of buspirone. The kobs of bergamottin for CYP3A was calculated based on the portal unbound Cmax. 3. Co-administration of bergamottin significantly increased the AUC0-inf for buspirone and fexofenadine by 1.6-fold and 1.7-fold, respectively, indicating that bergamottin inhibited both CYP3A and P-gp. 4. Bergamottin pre-treatment significantly elevated the AUC0-inf of oral buspirone by 3.7-fold but exerted no effect on the pharmacokinetics of intravenous buspirone, indicating that bergamottin pre-treatment selectively inhibited CYP3A-mediated intestinal metabolism without affecting the hepatic CYP3A. These findings were supported by the result that the kobs (0.00000118 min-1) of bergam...
Source: Xenobiotica - Category: Research Authors: Tags: Xenobiotica Source Type: research