论文部分内容阅读
目的 通过考察CYP3A的变化对大鼠体内紫杉醇代谢的影响 ,评价紫杉醇与其它可能合用的药物之间的相互作用。方法 本研究将 135只♀Wistar大鼠随机分入空白组、诱导组或抑制组。各组CYP3A的水平由于使用诱导剂或抑制剂而有所不同。大鼠尾静脉注射紫杉醇 10mg·kg-1后 ,采集动态血浆标本 ,以HPLC测定血药浓度 ,采用PCNONLIN程序进行房室模型数据拟合。结果 大鼠CYP3A被诱导和抑制时 ,紫杉醇代谢发生了明显的改变。空白对照组 ,诱导剂组和抑制剂组的cmax分别为 6 8.91,5 6 .5 1和 10 8.5 3μg·ml-1,AUC为 82 .48,5 3.96和 189.47μg·h·ml-1,而CL则为 0 .0 2 42 ,0 .0 37和 0 .0 10 5L·h-1。结论 大鼠CYP3A亚族在紫杉醇生物转化过程中起着重要作用。对酶作用的认识有利于预测并控制药物不良反应和可能的药物相互作用
Objective To investigate the effect of CYP3A on paclitaxel metabolism in rats and to evaluate the interaction between paclitaxel and other possible drugs. Methods In this study, 135 Wistar rats were randomly divided into blank group, induction group and control group. The levels of CYP3A in each group vary depending on the inducer or inhibitor used. After intravenous injection of paclitaxel (10mg · kg-1) into the tail vein of rats, dynamic plasma samples were collected to determine plasma concentration by HPLC. PCNONLIN program was used to fit the data of atrioventricular model. Results When the CYP3A was induced and inhibited in rats, the metabolism of paclitaxel changed obviously. The cmax values of the blank control group, the inducer group and the inhibitor group were 6 8.91,5 6 .5 1 and 10 8.5 3 μg · ml -1, respectively, and the AUCs were 82.48, 53.96 and 189.47 μg · h · ml -1, While CL is 0 .0 2 42, 0 .0 37 and 0 .0 10 5L · h-1. Conclusion The rat CYP3A subfamily plays an important role in paclitaxel bioconversion. Knowledge of the role of enzymes facilitates the prediction and control of adverse drug reactions and possible drug interactions