甘草对高脂血症大鼠模型洛伐他汀药代动力学的影响

Effects of Licorice on Pharmacokinetics of Lovastatin in Hyperlipidemic Rats

目的研究高脂血症大鼠模型中甘草对洛伐他汀药代动力学过程的影响。方法将18只SD大鼠随机分为对照组(n=6)和实验组(n=12)。实验组采用高脂饲料喂养大鼠,构建高脂血症大鼠模型,随机分为洛伐他汀单独给药组(n=6)和洛伐他汀与甘草联合给药组(n=6)。联合给药组给予甘草颗粒,单独给药组给予相应体积的生理盐水,连续7 d后,2组大鼠单剂量灌胃给予洛伐他汀胶囊(20 mg/kg,0.5%CMC-Na溶液)。分别于给药前和给药后不同时间点采集血浆样品,采用液相色谱-质谱联用方法测定血药浓度,计算药代动力学参数,并进行组间比较。结果长期给予甘草导致洛伐他汀代谢产物洛伐他汀酸在高脂血症大鼠中血浆暴露水平显著升高,联合给药组平均C_(max)较单独给药组升高约80%(P<0.05),而AUC0-t和AUC0-∞分别升高115%和109%(P=0.005和P=0.027)。联合给药组与单独给药组比较,洛伐他汀的C_(max)和AUC增加,但无统计学差异(P>0.05)。结论甘草可抑制洛伐他汀在高脂血症大鼠体内的代谢,增加其体内暴露水平。

Objective To study the effect of licorice on the pharmacokinetics of lovastatin in hyperlipidemic rat model. Methods Eighteen rats were randomly divided into control group（n = 6）and test group（n = 12）. Rats in the test group were administered high fat diet to construct hyperlipidemic rat model. The 12 hyperlipidemic rats were then randomly divided into two groups：lovastatin group（n = 6）and lovastatin combined with licorice group（n = 6）. The rats in both groups were administered lovastatin capsule（20 mg/kg,0.5% CMC-Na solution）after receiving licorice（for lovastatin combined with licorice group）or saline（for lovastatin group）for 7 days. Blood samples were collected at different time points before and after the administration of lovastatin capsule. The plasma concentrations of lovastatin and lovastatin acid（an active metabolite of lovastatin）were determined by LC-MS/MS method. Pharmacokinetics parameters were calculated using DAS 2.0 software,and the two groups were compared using SPSS 18.0 software. Results Long-term administration of licorice resulted in a significant increase in the plasma level of lovastatin acid in the hyperlipidemic rat,and the corresponding mean Cmax was approximately 80% higher than that of the lovastatin group（P 〈 0.05）,while AUC0-tand AUC0-∞ increased by 115% and 109%,respectively（P = 0.005 and P = 0.027）. Cmax and AUC of lovastatin also increased,but there was no statistical significance（P 〉 0.05）. Conclusion Licorice can inhibit the metabolism of lovastatin in hyperlipidemic rats and increase its exposure in vivo.