盐酸丁咯地尔在动物体内的药物动力学及组织分布研究

Pharmacokinetics of buflomedil hydrochloride in rabbits and tissue distribution in rats

目的:用高效液相色谱法测定家兔和大鼠静脉注射盐酸丁咯地尔后血清及组织器官中的药物浓度,进行药物动力学及组织分布研究。方法:样品在碱性条件下经有机溶剂萃取后在硅胶柱上用含樟脑磺酸的甲醇洗脱,检测波长275nm。结果:测得的血药浓度数据用PK-GPAPH程序拟合,主要参数为K12(h-1)=1.810±0.273,K21(h-1)=0.802±0.184,K10(h-1)=0.431±0.045,Vc(L/kg)=1.250±0.553,T1/2α(h)=0.2600.029,T1/2β(h)=6.017±0.681。静脉注射10min后脾和肾中浓度最高。结论:盐酸丁咯地尔静脉注射后在体内分布广泛,药物动力学符合二室开放模型。

Objective:To observe pharmacokinetics and tissue distribution of buflomedil hy-drochloride in rabbits and rats after iv injection by high performance liquid chromatographic method.Meth ods:The drug in serum or in tissue was extracted into the organic solvent under basic condition.The extracts were analyzed subsequently on a column packed with silica which contained camphorsul-phonic acid in methanol as mobile phase,the detection wavelength was275nm.Re sults:The detected data of drug in serum were analyzed by PK-GPAPH program and the main pharmacokinetic parameters were:K 12 (h -1 )=1.810±0.273,K 21 (h -1 )=0.802±0.184,K 10 (h -1 )=0.431±0.045,Vc(L/kg)=1.250±0.553,T 1/2α (h)=0.260±0.029,T 1/2β (h)=6.017±0.681.The highest concentration in tissue appeared in spleen and kidney after a single iv of10mg ·kg -1 in rats.Conclu sion:The concentration-time curve in rabbits is in accord with2-compartment open model.Tissue distribution studies showes extensive uptake in organs.