Zhao Xiufen, Wu Yan, Wang Dongmei
Department of Obstetrics and Gynecology, Qingdao Hiser Medical Group, Qingdao, 266033, Shandong, China.
Eur J Drug Metab Pharmacokinet. 2018 Feb;43(1):63-68. doi: 10.1007/s13318-017-0423-0.
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.
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.
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.
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.
据报道，土槿皮乙酸具有广泛的药理活性。本研究考察甘草酸对大鼠中土槿皮乙酸药代动力学的影响。
研究了口服土槿皮乙酸（2mg/kg），同时或不进行甘草酸预处理（剂量为100mg/kg/天，共7天）的药代动力学。采用灵敏可靠的液相色谱-串联质谱法测定土槿皮乙酸的血浆浓度，并计算和比较药代动力学曲线。此外，还进行了Caco-2细胞转运模型和大鼠肝微粒体孵育实验以研究其潜在机制。
结果表明，当大鼠用甘草酸预处理时，土槿皮乙酸的最大浓度（Cmax）从186.43±14.18降至124.62±18.49ng/mL，浓度-时间曲线从零至无穷大的面积（AUC）也从918.54±144.72降至504.72±115.63μg·h/L。土槿皮乙酸的消除半衰期（t1/2）值从3.16±1.18降至1.88±0.76小时（P<0.05）。Caco-2细胞转运实验表明，甘草酸可使土槿皮乙酸的外排率从2.39提高至3.64，大鼠肝微粒体孵育实验表明，甘草酸可使其内在清除率从51.87±5.34显著提高至76.79±8.52μL/min/mg蛋白。
总之，这些结果表明甘草酸可影响土槿皮乙酸的药代动力学，其作用机制可能是通过诱导P-糖蛋白活性降低土槿皮乙酸的吸收，或通过诱导细胞色素P450酶活性提高大鼠肝脏中的清除率。
