Effects of Glycyrrhizic Acid on the Pharmacokinetics of Pristimerin in Rats and its Potential Mechanism.

BACKGROUND AND OBJECTIVES

Pristimerin has been reported to possess a wide range of pharmacological activities. This study investigates the effects of glycyrrhizic acid on the pharmacokinetics of pristimerin in rats.

METHODS

The pharmacokinetics of orally administered pristimerin (2 mg/kg) with or without glycyrrhizic acid pretreatment (at a dose of 100 mg/kg/day for 7 days) were investigated. The plasma concentration of pristimerin was determined using a sensitive and reliable LC-MS/MS method, and the pharmacokinetics profiles were calculated and compared. Additionally, Caco-2 cell transwell model and rat liver microsome incubation experiments were also conducted to investigate its potential mechanism.

RESULTS

The results showed that when the rats were pretreated with glycyrrhizic acid, the maximum concentration (C ) of pristimerin decreased from 186.43 ± 14.18 to 124.62 ± 18.49 ng/mL, and area under the concentration-time curve from zero to infinity (AUC) also decreased from 918.54 ± 144.72 to 504.72 ± 115.63 μg·h/L. The elimination half-life (t ) value of pristimerin decreased from 3.16 ± 1.18 to 1.88 ± 0.76 h (P < 0.05). The Caco-2 cell transwell experiments indicated that glycyrrhizic acid could increase the efflux ratio of pristimerin from 2.39 to 3.64, and the rat liver microsome incubation experiments showed that glycyrrhizic acid could significantly increase its intrinsic clearance rate from 51.87 ± 5.34 to 76.79 ± 8.52 µL/min/mg protein.

CONCLUSIONS

In conclusion, these results indicated that glycyrrhizic acid could affect the pharmacokinetics of pristimerin, and it might work through decreasing the absorption of pristimerin by inducing the activity of P-gp or through increasing the clearance rate in rat liver by inducing the activity of cytochrome P450 enzyme.