The effect of quercetin on the pharmacokinetics of verapamil and its major metabolite, norverapamil, in rabbits

We have investigated the effect of quercetin on the pharmacokinetics of verapamil and its major metabolite, norverapamil, in rabbits. Pharmacokinetic parameters of verapamil and norverapamil were determined after the oral administration of verapamil (10 mg kg^-1) to rabbits in the presence and absence of quercetin (5.0 and 15 mg kg^-1). While co-administration of quercetin concurrently was not effective to enhance the oral exposure of verapamil, pretreatment of quercetin 30 min before verapamil administration significantly altered the pharmacokinetics of verapamil. Compared with the control group (given verapamil alone), the C_max and AUC of verapamil increased approximately twofold in the rabbits pretreated with 15 mg kg^-1 quercetin. There was no significant change in T_max and terminal plasma half-life (t1/2) of verapamil in the presence of quercetin. Consequently, absolute and relative bioavailability values of verapamil in the rabbits pretreated with quercetin were significantly higher (P<0.05) than those from the control group. Metabolite-parent AUC ratio in the rabbits pretreated with quercetin decreased by twofold compared with the control group, implying that pretreatment of quercetin could be effective to inhibit the CYP3A4-mediated metabolism of verapamil. In conclusion, pretreatment of quercetin significantly enhanced the oral exposure of verapamil. This suggested that concomitant use of quercetin or a quercetin-containing dietary supplement with verapamil requires close monitoring for potential drug interaction.