1. Puerarin has been reported to possess a wide range of pharmacological activities. This study investigated the effects of glycyrrhizin on the pharmacokinetics of puerarin in rats. 2. The pharmacokinetics of orally administered puerarin (50 mg/kg) with or without glycyrrhizin pretreatment (100 mg/kg/day for 7 days) were investigated. The plasma concentration of puerarin was determined using a sensitive and reliable LC-MS/MS method. The pharmacokinetics profiles were calculated and compared. Additionally, a Caco-2 cell transwell model was used to investigate the potential mechanism of glycyrrhizin's effects on the pharmacokinetics of puerarin. 3. The results showed that when the rats were pretreated with glycyrrhizin, the maximum concentration (Cmax) of puerarin decreased from 761.25 ± 52.34 to 456.32 ± 34.75 ng/mL, and the area under the concentration-time curve from zero to infinity (AUC0-inf) also decreased from 4142.15 ± 558.51 to 2503.74 ± 447.57 μg·h/L. The oral clearance of puerarin increased significantly from 12.20 ± 1.53 to 20.47 ± 3.25 L/h/kg (p < 0.05). The Caco-2 cell transwell experiments indicated that glycyrrhizin could increase the efflux ratio of puerarin from 1.88 to 3.14. 4. In conclusion, these results indicated that glycyrrhizin could affect the pharmacokinetics of puerarin, possibly by decreasing the systemic exposure of puerarin by inducing the activity of P-gp.
Keywords: Glycyrrhizin; LC-MS/MS: Caco-2 cell; pharmacokinetics; puerarin.