Abstract
Radix astragali and puerarin are always used together for cardiovascular disease in China clinics. This study investigates the effects of astragaloside IV (AS-IV, the main components of radix astragali) on the pharmacokinetics of puerarin in rats. The pharmacokinetics of orally administered puerarin (50 mg/kg) with or without AS-IV pretreatment (100 mg/kg/day for seven 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 AS-IV on the transport pf puerarin. The results showed that when the rats were pretreated with AS-IV, the maximum concentration (Cmax) of puerarin decreased from 760 to 467 ng/mL (p < .05, n = 6, 90% CI, 293 ± 61.28), and the area under the concentration-time curve from zero to infinity (AUC0-inf) also decreased from 4097 to 2330 μg·h/L (p < .05, n = 6). The oral clearance of puerarin increased significantly from 11.9 to 22.4 L/h/kg (p < .05, n = 6). The Caco-2 cell transwell experiments indicated that AS-IV could increase the efflux ratio of puerarin from 1.81 to 2.79 through inducing the activity of P-gp. In conclusion, these results indicated that AS-IV could affect the pharmacokinetics of puerarin, possibly by decreasing the systemic exposure of puerarin by inducing the activity of P-gp.
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