The aim of this study was to determine the effects of garlic and ginkgo herbal extracts on the pharmacokinetics of the P-glycoprotein (P-gp)/Organic anion transporting polypeptides (Oatps) substrate fexofenadine. Male rats were dosed orally with garlic (120 mg/kg), ginkgo (17 mg/kg), St. John's wort (SJW; 1000 mg/kg; positive control) or milli Q water for 14 days. On day 15, rats were either administered fexofenadine (orally or intravenously), had their livers isolated and perfused with fexofenadine, or the small intestine divided into four segments (SI-SIV) and analysed for P-gp and Oatp1a5. In vivo, SJW increased the CL of fexofenadine by 28%. Garlic increased the AUC0-∞ and Cmax of fexofenadine by 47% and 85%, respectively. Ginkgo and SJW had no effect on the oral absorption of fexofenadine. In the perfused liver, garlic, ginkgo and SJW increased the biliary clearance of fexofenadine with respect to perfusate by 71%, 121% and 234%, respectively. SJW increased the biliary clearance relative to the liver concentration by 64%. The ratio of liver to perfusate concentrations significantly increased in all treated groups. The expression of Oatp1a5 in SI was increased by garlic (88%) and SJW (63%). There were no significant changes in the expression of P-gp. Induction of intestinal Oatp1a5 by garlic may explain the increased absorption of orally administered fexofenadine. Ginkgo had no effect on the expression of intestinal P-gp or Oatp1a5. A dual inductive effect by SJW on opposing intestinal epithelial transport by Oatp1a5 and P-gp remains a possibility.
- drug absorption
- drug-drug interactions
- efflux transporters (P-gp, BCRP, MRP, MATE, BSEP, etc)
- gastrointestinal tract
- natural products
- Uptake transporters (OATP, OAT, OCT, PEPT, MCT, NTCP, ASBT, etc.)
- The American Society for Pharmacology and Experimental Therapeutics