盐酸小檗碱在Beagle狗静脉注射和口服药动学研究

Studies on the intrvenous pharmacokinctics and oral absorbtion of berberine HCI in beagle dogs

传统观念认为小檗碱口服吸收差,而近年来,临床口服小檗碱用来治疗心律失常及充血性心衰.为解决其中的矛盾,本实验建立了HPLC方法(最低检测限为2μg·L^(-1))研究Beagle狗po和iv小檗碱的药代动力学、100 mg静脉注射的药—时曲线符合二室模型,K.为10.18 h^(-1),T_(1/2u)为0·15·h^(-1)T_1/2β为12.59·h^(-1),CL为60.70 L·h^(-1),AUC达1979.31 μg·L^(-1)V_d为699.53L。280 mg·kg^(-1)组发生呕吐·仅一狗可计算P—K参数,T_(max)为3.71h,C_(max)为15.46 μg·L^(-1),AUC为777.29μg·h^(-1)·L^(-1).T T_(1/za)0.63 h·T_(1/z)el34.82h,V_a为125.41L,K.为0.02·h^(-1),CL为2.64 L·h^(-1),45 mg·kg^(-1)一次口服以及45 mg·kg^(-1)Bid连续给药1wk的血药浓度都在10μg·L^(-1)以下。700 mg·kg^(-1)组因发生严重呕吐.腹泻,药物吸收差.血浓度在10 μg·L^(-1)以下,不能计算P—K参数.

It is a conventional point of view that berberine is poorly absorbed following oral administration. But in recent years berberine is orally used in clinical practice for the treatment of arrhythmia and congestive heart farlure. In order to solve the problem, this paper established a HPLC method (limit of quantification is 2μg · L-1), to study the pharmacokinetic property of berberine in Beagle dogs. P-K curves of 100 mg intravenous injection is a two-compartment model with its K. 10. 18·h-1, T1/2α0. 15h, T 1/2β12. 59h, CL 60.70 L · h-1,AUC 1979.31 μg · h-1 · L-1and Vd 699. 53 L. Vomiting happened after 280 mg · kg-1oral administration group. Its T max is 3. 17 h, C max 15. 46μg·L-1, AUC 777. 29 Mg · h-1 · L-1, Vd 125. 41 L, Ke 0. 02·h-1and CL 2. 64 L · h-1. The plasma concentrations after 45 mg · kg-1 given orally are always below 10 mg v L-1. So are the concentration after 45 mg · kg-1 orally given two times a day for one week. Severe Vomiting and diarrhea happened in all dogs of 700 mg · kg-1 oral adminstration group,so the plasma concentration is below 1 0 ng · L-1and its P-K parameters can't be determined.