Effects of astragaloside IV on the pharmacokinetics of puerarin in rats

Abstract

1. Radix astragali and puerarin are always used together for cardiovascular disease in China clinics.

2. This study investigates the effects of astragaloside IV (AS-IV, the main components of radix astragali) on the pharmacokinetics of puerarin in rats.

3. 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.

4. The results showed that when the rats were pretreated with AS-IV, the maximum concentration (C_max) 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 (AUC_0–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.

5. 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.

Keywords:

• Drug–drug interaction
• P-gp: Caco-2 cell

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This study was funded by Talent-development Project of Pudong Health and Family Planning Commission of Shanghai (PWRd 2014-16), and Shanghai Municipal Commission of Health and Family Planning [201540126].