海藻玉壶汤及其加味的药代动力学研究

Pharmacokinetics studies of Haizao Yuhu decoction and its modified prescriptions

为了探讨海藻与甘草配伍比例及海藻玉壶汤加味对海藻玉壶汤药动学的影响,将中药药物代谢动力学中多点动态测定的原理与动物死亡率测定药物蓄积性的方法相结合。结果海藻玉壶汤一号方、二号方和三号方在小鼠体内呈一级动力学消除,一室模型。一号方、二号方和三号方的半数致死量分别为8316.039 mg/kg、6177.153 mg/kg和7347.516 mg/kg,表观吸收半衰期(t1/2Ka)分别为0.001 h、0.0003 h和0.0020 h,表观消除半衰期(t1/2Ke)分别为77.407 h、31.485 h和26.532 h,达峰时间(Tp)分别为0.710 h、0.075 h和0.969 h,平均滞留时间(MRT)分别为11.628 h、29.785 h和10.738 h,AUC分别为247.532、74.033和92.047 mg.h.l-1。海藻与甘草配伍比例变化会导致海藻玉壶汤毒性和药代动力学特征变化,通过加入逍遥散部分药物能消除由海藻与甘草配伍比例改变造成的动力学特征的变化。

Several groups of rats were given Haizao Yuhu deeoction（Ⅰ）and two modification of it（Ⅱ,Ⅲ）to study the pharmacokinetion of them with the theory of multf-point dynamic test.and pharmaceutical accumulative method,which was usally used to measure the death rates of animals.The results were as follows;The LD50 of Ⅰ,Ⅱ,Ⅲ was 8316.039mg/kg,6177.153mg/kg and 7347.516mg/kg,and their pharmacnkinetics model were 1-compartment model with 1st order absorption,the t1/2kα,and t1/2kα,was 0.001h,0.0003h,0.002h and 77.407h,31.485h and 26.532h in turn.Meanwhile the MRT of there prescriptions was 11.628h,29.785h and 10.738h,and AUC was 247.532,74.033 and 92.047mg·h·l^-1,respectively.These suggested that different proportion of Haizao and Gancao would lead to some changes on pharmacokinetics characteristics of Haizao Yuhu decoction,but this changes would be partly climinate by some ingredients after which were added to decoction Ⅱ.