CYP3A酶活性与紫杉醇血药浓度的相关性探讨

Investigation of correlation between CYP3A activity and plasma concentration of paclitaxel

目的建立肿瘤患者紫杉醇给药后血浆药物浓度的测定方法,并研究患者个体内CYP3A酶活性与紫杉醇血药浓度之间的相关性。方法采用HPLC法,分别测定20例肿瘤患者血浆紫杉醇浓度及尿液CYP3A酶活性,采用两变量Bivarite法进行相关性分析。结果紫杉醇个体血药浓度范围为0.2～5.83mg·mL-1,相差近30倍;紫杉醇血药浓度与CYP3A酶活性常用对数(lgCYP3A酶活性)线性相关,r=0.9381。结论紫杉醇血药浓度个体差异大,临床有必要进行血药浓度监测;通过测定CYP3A酶活性制定紫杉醇给药方案是可行的。

AIM To establish a method for the determination of paclitaxel in tumor patient＇ s plasma and to investigate the correlation between drug concentration and CYP3A activity. METHODS The concentration of paclitaxel in plasma and hydrocortisone, 6β-hydroxycortisol in urine were determined by HPLC, respectively. The urinary ratio of 6β- hydroxycortisol/hydrocortisone had been used as a noninvasive scale for human CYP3A activity. The concentration of paclitaxel was assessed with CYP3A activity to do correlative analysis. RESULTS Concentration of paclitaxel in plasma varied from 0.2 to 5.83 mg· L^- 1, which showed a good correlation with lgCA, r = 0. 938 1. CONCLUSION It is necessary to monitor the concentration of paclitaxel in tumor patients and it is feasible to determine the paclitaxel therapeutic schedule through detection of CYP3A.