Pharmacokinetic interactions of clopidogrel with quercetin, telmisartan, and cyclosporine A in rats and dogs

In this study, we investigated pharmacokinetic drug interactions of clopidogrel with P-gp inhibitors in rats and dogs. Following the oral administration of clopidogrel with or without the P-gp inhibitors, quercetin (250 mg/kg), telmisartan (8 mg/kg), and cyclosporine A (10 mg/kg), in rats and dogs, the plasma concentration-time profiles of clopidogrel carboxylic acid, a surrogate marker for the bioavailability of clopidogrel, were determined. Co-administration of the quercetin, telmisartan and cyclosporine A significantly increased the area under the curve and peak plasma concentration of clopidogrel carboxylic acid in rats. However, in dogs, the plasma concentrations of clopidogrel carboxylic acid were not considerably changed by the coadministration of three different kinds of P-gp inhibitors. These findings suggest potential interaction of clopidogrel with quercetin, telmisartan, and cyclosporine A, although there are differences between animal models. Follow-up clinical study is needed to explore the meaning of this remarkable species differences in the P-gp-mediated interaction.