大鼠体内桃核承气汤蒽醌类药代动力学研究

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目的研究桃核承气汤中蒽醌类成分在大鼠体内药代动力学规律.方法大鼠灌胃给予桃核承气汤5、10 g.kg-1后,采集血浆、尿和胆汁,用HPLC方法分析样品中蒽醌类成分、测定血浆中大黄酸浓度经时变化,浓度-时间数据用3P97药代动力学软件进行分析,计算药动学参数.结果大鼠灌胃给予桃核承气汤后,血浆中检测到芦荟大黄素、大黄酸、大黄素,尿中检测到芦荟大黄素、大黄酸、大黄素和大黄酚,胆汁中检测到大黄酸和大黄酚;血液、尿液和胆汁中均以大黄酸含量最高,且经尿排泄的量明显多于经胆汁排泄的量.灌服桃核承气汤5和10 g.kg-1剂量组,T12(α)为0.03和0.13 h,T12(β)为1.46和2.51 h,T12(Ka)为0.01和0.12 h,V1为0.14和0.12 L.kg-1,CL为0.77和0.33 L.h-1.kg-1,Cm ax为(2.15±0.29)和(9.70±2.50)mg.L-1,Tpeak为(0.19±0.04)和(0.23±0.04)h,AUC0-∞为1.69和6.50 mg.L-1.h.结论桃核承气汤中蒽醌类成分可以吸收进入体内,其中以大黄酸为主;体内蒽醌类成分经尿和胆汁排泄,其中以尿排泄为主.大鼠灌服桃核承气汤,血浆中大黄酸浓度时间过程符合二室开放模型.“,”Aim To study the pharmacokinetics of anthraquinones in rats after ig of Taohechengqi decoction.Methods SD rats were given a single ig dose of Taohechengqi decoction 5 or 10 g·kg-1.Anthraquinone components in plasma,urine and bile were analysed and plasma concentrations of rhein were measured with HPLC after extracted with perchloric acid and ether.Pharmacokinetic parameters were determined from the plasma concentration-time data with the 3P97 software package.Results After ig Taohechengqi decoction in rats,aloe-emodin,rhein and emodin were detected in plasma;aloe-emodin,rhein,emodin and chrysophanol were detected in urine and rhein and chrysophanol were detected in bile.The rhein concentration was the highest of all anthraquinones in all plasma,urine and bile samples.The amount of rhein excreted through urine was higher than that excreted through bile.After a single ig dose of Taohechengqi decoction 5 and 10 g·kg-1,T12(α) were 0.03 and 0.13 h,T12(β) were 1.46 and 2.51 h,T12(Ka) were 0.01 and 0.12 h,V1 were 0.14 and 0.12 L·kg-1,CL were 0.77 and 0.33 L·h-1·kg-1,Cmax were 2.15±0.29 and 9.70±2.50 mg·L-1,Tpeak were 0.19±0.04 and 0.23±0.04 h,AUC0-∞ were 1.69 and 6.50 mg·L-1·h,respectively.Conclusion Anthraquinones(mainly rhein) can be absorbed after ig administration of Taohechengqi decoction in rats.The anthraquinones are mainly excreted through urine and,to a less extent,through bile in rats.The time course of rhein in plasma in rats complies with a two-compartment model.
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