摘要
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.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2011年第6期643-646,共4页
Chinese Journal of Clinical Pharmacology and Therapeutics
基金
国家自然科学基金(30528026
30300428
30672497
30500623)
纽约中华医学会基金(01-755)