口服马钱子碱后小鼠体内的药动学研究

Study on Pharmacokinetics of brucine in mice

目的 研究马钱子碱在小鼠体内的药动学。方法 小鼠灌胃 2种剂量 6 0及 4 0mg·kg- 1 后用荧光分光光度法测定不同时间的血药浓度和组织浓度。应用 3P87药动学软件程序对数据进行计算机处理。结果 2种剂量的主要动力学参数 :Ka分别为 3 5 6和 4 3h- 1 ;Ke分别为 0 5 4和 0 5 9h- 1 ;t1 2Ka分别为 0 19和 0 16h ;t1 2Ke分别为 1 2 8和 1 17h ;VC 分别为 14 5 9和13 37L·kg- 1 ;CLs 分别为 7 87和 7 89L·h- 1 ·kg- 1 ;AUC分别为 7 6 2和 5 0 7h·mg·L- 1 。组织中以肝脏浓度最高 ,然后依次是肾、心、肺和脑 ,血中浓度最低。结论 2种剂量马钱子碱在小鼠体内的C T变化均符合一室开放模型 ,马钱子碱在小鼠体内分布 ,消除迅速。

OBJECTIVE: To study the pharmacokinetics of brucine in mice. METHODS: After intragastric administraction of brucine at doses of 60 and 40 mg&middotkg -1 in mice, the plasma and tissue concentrations at differnet timepoints were determined by fluorescence spectrophotometry. The data were processed with 3P87 pharmacokinetic program. RESULTS: The pharmacokinetic parameters of the two doses were as follows: Ka were 3.56 and 4.31 h -1; Ke were 0.54 and 0.59 h-1; t1/2Ka. were 0.19 and 0.16 h, t1/2Ke, were 1.28 and 1.17 h; Vc were 14.59 and 13.37 L&middotkg-1; CLs were 7.87 and 7.89 L&middoth-1&middotkg-1; AUC were 7.62 and 5.07 h&middotmg&middotL-1, respectively. The brucine concentration in the liver was the highest and those in the kidney, heart, lung, brain and plasma decreased sequentially. CONCLUSION: At doses of 60, 40 mg&middotkg -1 in mice, the concentration-time curves of brucine were found to be fitted to one-compartment open model with first order absorption. The distribution and elimination were rapid.