槲皮素对辛伐他汀药动学的影响

Effects of quercetin on pharmacokinetics of simvastatin

目的:观察中药有效成分槲皮素对辛伐他汀药动学的影响。方法:家兔10只,随机分为2组,一组口服给予槲皮素溶液10 mg·kg-1,另一组口服给予同体积的生理盐水,qd,连续10 d。末次给予槲皮素溶液2 h后,家兔分别口服给予辛伐他汀。血浆用环己烷-二氯甲烷(体积比为3.5∶1)提取,以洛伐他汀为内标,在237 nm波长下检测;色谱柱Lichrosorb C18(200mm×4.6 mm,5μm);流动相乙腈-水(体积比为60∶40);流速1.2 mL·min-1。结果:辛伐他汀血药浓度在0.25～100.0μg·L-1范围内样品峰面积与内标峰面积的比值之间线性关系良好,日内及日间相对标准偏差分别低于2.65%和3.30%,回收率高于95.23%。药动学参数显示,给予槲皮素后,辛伐他汀清除率明显降低,最大血药浓度显著增加,达对照组的2.44倍。虽然最大达峰时间没有明显改变,但辛伐他汀血药浓度在体内的维持时间明显延长。结论:槲皮素与辛伐他汀联合用药时,可明显延缓辛伐他汀的代谢。

OBJECTIVE To determine the effects of quercetin on the pharmacokinetic parameters of simvastatin with HPLC method. METHODS A total of 10 rabbits was randomly divided into 2 groups and assigned to receive a dose of 10 mg·kg^-1·d^-1 of quercetin and same volume of normal saline by oral administration for ten days. After the last intragastric administra- tion, the rabbits were given a single dose of 20 mg·kg^-1 of simvastatin by oral administration. Plasma samples were collected from jugular vein by arterial cannulae. Simvastatin and internal standard lovastatin in plasma were extracted with cyclohexane- dichloromethane （3.5：1）, and then measured by HPLC using a Lich rospher C18 column as stationary phase and an acetoni- trile-water （60：40） mixture as mobile phase. The flow rate was 1.2 mL·min^-1. Simvastatin was quantified by UV at 237 nm. RESULTS The calibration curve showed a good linearity in the mass concentration range of 0. 25--100.0μg·L^-1. The regres- sion equation was： Y = 0. 036 4C ＋ 0. 005 83, r = 0. 999 8. Intra-day and inter-day coefficients of variation of assay for simvas- tatin in plasma were less than 2. 65% and 3.3%, respectively. The recoveries of simvastatin were more than 95. 23%. From the pharmacokinetic parameters, we could see a significant increase in the maximum drug concentration, it was the 2. 44 times of control group. Although the T（peak） of simvastatin after giving quercetin was not changed significantly, but the effective drug duration extended significantly. CONCLUSION When quercetin combined with simvastatin was used, quercetin can de- layed the metabolism of simvastatin.