金雀异黄酮在体内对CYP3A活性的影响

Effects of genistein on cytochrome P450 3A activity in healthy volunteers

目的：阐明金雀异黄酮在体内对细胞色素氧化酶P-4503A（CYP3A）活性的影响。方法：本试验采用双周期交叉临床试验。临床试验按照两阶段交叉方案进行。第一阶段随机分成的2组受试者随机给予金雀异黄酮片或安慰剂处理14 d,第15天给所有受试者米哒唑仑探针药,经过14 d洗脱期后交叉重复试验,分别以0~36 h血浆中米哒唑仑的血浆曲线下面积、半衰期作为CYP3A的活性指标。HPLC测定其活性。服药后0~36 h血中咪达唑仑以及1＇-羟基咪达唑仑用HPLC-MS/MS方法测定。结果：经金雀异黄酮处理后,咪达唑仑AUC0-36 h明显降低[（144±55）ng.mL-1.hvs（126±40）ng.mL-1.h,P〈0.05],AUC0-∞显著降低[（209±57）vs（181±43）ng.mL-1.h,P〈0.05],Cmax显著降低[（49±20）vs（36±14）,P〈0.05]。结论：金雀异黄酮对体内CYP3A酶活性具有显著的诱导作用,应当关注经CYP3A代谢的药物与金雀异黄酮合用时可能发生的潜在的药物相互作用。

AIM：To examine the potential effects of genistein on CYP3A activity. METHODS： The experiment was conducted in an open,randomized,2-period crossover study.The probe drug midazolam was used as an indicator of CYP3A function.Every volunteer was administered orally,once a day for 14 days,genistein 1000 mg or placebo（control）.On 15th day,a 7.5 mg midazolam was administrated orally.The plasma concentration of midazolam,1-OH midazolam was determined over 36 h.RESULTS：Coadministration of genistein obviously decreased the area under the curve AUC0-36 of midazolam [（144±55） ng·mL-1·h vs（126±40） ng·mL-1·h,P0.05],and significantly decreased AUC0-∝ of midazolam[（209±57） vs（181±43） ng·mL-1·h,P0.05],and also decreased Cmax of midazolam[（49±20） vs（36±14）,P0.05].CONCLUSION： Genistein,a principal isoflavone in soybean,in regular doses may induce CYP3A activity in vivo,and it should be aware of potential drug-food interactions.