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10 mg·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c_max分别为68.91，56.51和108.53 μg·ml^-1，AUC为82.48，53.96和189.47 μg·h·ml^-1，而CL则为0.0242，0.037和0.0105 L·h^-1。结伦 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 identify the role of the hepatic CYP isoenzymes involved in paclitaxel biotransformation and to evaluate the metabolic drug interaction between paclitaxel and other anticancer agents. METHODS:The female wistar rats were pretreated with saline,dexamethasone or ketoconazole respectively before paclitaxel,and their levels of CYP3A were determined.Then 135 rats received paclitaxel at dose level of 10 mg·kg^-1(iv).Nine plasma samples were obtained up to 12 hours after injection.Paclitaxel were quantified by HPLC.Their pharmacokinetics were assessed by noncompartment model and model-dependent method,respectively. RESULTS:It was found that the c_maxvalue of 68.91,56.51 and 108.53 μg·ml^-1were obtained in controlled,induced and inhibited group,respectively.The Cl values (0.0242,0.037 and 0.0105 L·h^-1,respectively)were reached. CONCLUSION:It suggested that liver cytochrome P450 3A subfamily plays a major role in paclitaxel biotransformation.These finding may have clinical implications and should be taken into account in chemotherapy.