Effect of hesperidins on the pharmacokinetics of CPT ‐11 and its active metabolite SN‐38 by regulating hepatic Mrp2 in rats

This study examined the effect of hesperidins on pharmacokinetics of CPT‐11 and SN‐38 as well as the regulatory effect on hepatic expression of Mrp2. Comparing to the control group, the AUC5‐t was increased to 115% of CPT‐11 and 122% of SN‐38; the CL was decreased to 87% for CPT‐11; the tissue concentration was increased in the liver, kidney and colon; and the accumulated biliary excretion was significantly decreased to 77% for CPT‐11 and 76% for SN‐38 in hesperidins‐treated rats. Furthermore, the expression of Mrp2 in liver was significantly decreased to 37% in hesperidins‐treated rats when compared to that of the control group. These results indicate that oral administration of hesperidins significantly increased the AUC5‐t and reduced the clearance of CPT‐11 and SN‐38, possibly through decreasing hepatic expression of Mrp2, and thus inhibiting the biliary excretion of CPT‐11 and SN‐38. Results from this present study suggest that hesperidins may reduce the exposure of CPT‐11 and SN‐38 in the intestine by reducing the amount of biliary excretion of CPT‐11 and SN‐38.
Source: Biopharmaceutics and Drug Disposition - Category: Drugs & Pharmacology Authors: Tags: Original Paper Source Type: research