黄豆苷元对卡马西平及其代谢产物在大鼠体内药动学的影响

Effect of daidzein on the pharmacokinetics of carbamazepine and its metabolite in rats

目的:研究黄豆苷元对卡马西平及其代谢产物10,11-环氧卡马西平(CBZ-E)在大鼠体内药动学的影响。方法:16只大鼠随机分为实验组和对照组,实验组大鼠连续10 d灌胃给予黄豆苷元100 mg.kg-1,对照组大鼠则灌胃给予等体积的生理盐水,两组大鼠第11天分别灌胃给予卡马西平10 mg.kg-1,于给药后不同时间点采血,采用HPLC法测定血浆中卡马西平及其代谢产物CBZ-E的浓度,计算药动学参数。结果:与对照组相比,实验组大鼠血浆中卡马西平的AUC0-24h、AUC0-∞、Cmax和t1/2显著增加(P<0.05),代谢产物CBZ-E的AUC0-24h、AUC0-∞和Cmax显著降低(P<0.05)。结论:黄豆苷元连续给药后改变了卡马西平在大鼠体内的药动学特征,可能与抑制CYP3A4的活性有关。

OBJECTIVE To investigate the effect of daidzein on the pharmacokinetics of carbamazepine（CBZ） and its metabolite 10,11-carbamazepine-epoxide（CBZ-E） in rats.METHODS Sixteen rats were divided into two groups randomly,then the experimental group rats were orally administered with daidzein（100 mg·kg^-1） for ten days consecutively and the control rats were given 0.9% saline solution at the same volume.On the 11th day,the two groups were given carbamazepine（10 mg·kg^-1） orally.Plasma concentration of the carbamazepine and its metabolite CBZ-E was determined by HPLC.Based on the data,the pharmacokinetic parameters were calculated.RESULTS Compared with the control group,the AUC0-24h,AUC0-∞ and Cmax of carbamazepine in the experimental group were significantly increased（P〈0.05）,what＇s more,the AUC0-24h,AUC0-∞,Cmax and t1/2 of the metabolite were greatly decreased（P〈0.05）.CONCLUSION The metabolism of carbamazepine in rat was greatly changed by daidzein.The underlying mechanism may be related to the inhibition on the activity of CYP3A4 by daidzein.