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Effects of verapamil on the pharmacokinetics of puerarin in rats

Abstract The oral bioavailability of puerarin is poor which hindered its clinical performance. This study investigates the effects of verapamil on the pharmacokinetics of puerarin in rats. The pharmacokinetics of orally administered puerarin (50 mg/kg) with or without verapamil pretreatment (10 mg/kg/day for 7 days) were investigated. The plasma concentration of puerarin was determined using LC-MS/MS method, and the pharmacokinetics profiles were calculated and compared. Caco-2 cell transwell model was also used to investigate the effects of verapamil on the transport pf puerarin. The results showed that when the rats were pretreated with verapamil, the maximum concentration (Cmax) of puerarin increased from 683.7 ± 51.2 to 933.5 ± 75.8 ng/mL (p < 0.05), and the area under the concentration-time curve from zero to infinity (AUC0-inf) also increased from 3687.3 ± 444.6 to 5006.1 ± 658.6 μg·h/L (p < 0.05). The Caco-2 cell transwell experiments indicated that verapamil could decrease the efflux ratio of puerarin from 1.90 to 1.19 through inhibiting the activity of P-gp. In conclusion, these results indicated that verapamil could affect the pharmacokinetics of puerarin, possibly by increasing the systemic exposure of puerarin by inhibiting the activity of P-gp.