川芎嗪药代动力学与药效学相关性及肝功能损伤对其药代动力学的影响

STUDY ON THE RELATIONSHIP BETWEEN PHARMACOKINETICS AND PHARMACODYNAMICS OF TETRAMETHYLPYRAZINE AND EFFECTS OF ACUTE HEPATIC POISONING ON ITS PHARMACOKINETICS IN RATS

大鼠静脉注射磷酸川芎嗪(TMPP)200mg/kg后,其药代动力学属二房室开放模型。给药后产生明显的抗血小板聚集及降压作用。经药效——药代动力学联合模型处理,求得其keo分别约为0.664/h和4.150/h,t_(1/2)keo约为1.04h及0.14h,EC_(50)约为113.00μg/ml及31.22μg/ml。体外实验证明,川芎嗪主要在肝脏代谢,CCl_4肝损伤后川芎嗪的t_(1/2)β延长,kel变小,ClP下降和血药浓度明显升高。

Serum level of tetramethylpyrazine (TMPZ) was determined by HPLC and the parameters ofrelationship between pharmacokinetics and pharmacodynamics of TMPZ were calculated by using thesoftware package of MCPKP and Sheiner's pharmacodynamic-pharmacokinetic modelling. The parame-ters in antiplatelet aggregation of TMPZ were keo 0.664/h, t^1/2 Keo 1.04 h and EC_(50) 11.300 μg/ml. Theparameters in hypotensive effect were Keo 4.15/h, t^1/2 Keo 0.14 h and EC_(50) 31.22 μg/ml respectively. The results demonstrated that CCl_4 hepatic injury significantly affected the elimination and distri-bution of TMPZ in rats. The t^1/2 B was delayed, the Kel, CLp, Vc and Vb were minimized and theAUC was much higher in comparison with the control group.