以咖啡因为代谢探针测定细胞色素P450 CYP2A6活性

细胞色素P450CYP2A6（CYP2A6）是体内重要的药物代谢酶之一，主要在肝脏表达，约占肝脏细胞色素P450酶的5％。CYP2A6参与抗肿瘤药（环磷酰胺和异环磷酰胺）、麻醉药（氟烷和甲氧氟烷）、前致癌物（黄曲霉素B1、亚硝胺盐等）、环境化合物（汽油醚）及烟草中尼古丁的代谢。CYP2A6活性与这些物质的疗效或毒性以及一些肿瘤的易感性密切相关，测定CY1Y2A6活性有助于预测药物疗效、预防药物毒副反应及肿瘤病因调查。

Determination of the activity of cytochrome P-450 CYP2A6 by HPLC method with caffeine as metabolizing probe

Aim To establish a HPLC method for determining five major metabolites of caffeine in the urine,5-acetylamino-6-formylamino-3-methyluracil(AFMU),1-methylxanthine(1X),1-methyluric acid(1U),1,7-dimethyluric acid(17U) and 1,7-dimethylxanthine(17X) and assess the activity of cytochrome P-450 CYP2A6.Methods The contents of five major metabolites of caffeine in the urine were determined by RP-HPLC method.Frequency distribution histogram was drawn by calculating the 17U/(AFMU+1X+1U+17X+17U) and then evaluated the activity of CYP2A6.Results The frequency distribution histograms of CYP2A6 approximately indicated three distinct groups,the cut of point is 0.23 between fast metabolizer and intermediate type.And the cut of point is 0.15 between slow metabolizer and intermediate type.Conclusion The method is simple and rapid,suitable for the determination of metabolites of caffeine in urine.The method can be used to assay the activity of CYP2A6.