Sharma Ashish, Pilote Sylvie, Bélanger Pierre M, Arsenault Marie, Hamelin Bettina A
The Québec Heart and Lung Institute, Laval Hospital, Québec, Canada.
Br J Clin Pharmacol. 2004 Sep;58(3):288-97. doi: 10.1111/j.1365-2125.2004.02162.x.
To assess the feasibility of administering at the same time low doses of five probe drugs, metoprolol (25 mg), chlorzoxazone (250 mg), tolbutamide (250 mg), dapsone (100 mg) and caffeine (100 mg) to determine simultaneously the activities of CYP2D6, CYP2E1, CYP2C9, CYP3A4, CYP1A2, N-acetyltransferase-2 and xanthine oxidase.
Ten healthy young non-smoking males received the following drugs or combinations of drugs over a 5-week period: week 1) metoprolol; 2) tolbutamide; 3) caffeine, chlorzoxazone and dapsone; 4) caffeine, chlorzoxazone, dapsone and metoprolol; 5) caffeine, chlorzoxazone, dapsone, metoprolol and tolbutamide. The drugs were self-administered at bedtime and urine was collected for the following 8 h.
Mean molar phenotypic ratios obtained after administering metoprolol (mean change of -11%) or tolbutamide (mean change of -0.3%) alone, were not significantly different from those obtained when other drugs were co-administered (P > 0.05). The mean within-subject coefficients of variation were 33%, 18%, 22%, 13%, 16%, 13% and 5% for CYP3A4, CYP2D6, CYP2C9, CYP2E1, CYP1A2, N-acetyltransferase 2 and xanthine oxidase metabolic ratios, respectively. No significant interactions (P > 0.5) were observed during the simultaneous administration of various combinations of the five probe drugs.
We propose that this cocktail, composed of five widely available drugs, constitutes a promising means of simultaneously determining the activities of the major CYP enzymes in large populations.
评估同时给予低剂量的五种探针药物（美托洛尔25毫克、氯唑沙宗250毫克、甲苯磺丁脲250毫克、氨苯砜100毫克和咖啡因100毫克）以同时测定CYP2D6、CYP2E1、CYP2C9、CYP3A4、CYP1A2、N - 乙酰转移酶 - 2和黄嘌呤氧化酶活性的可行性。
10名健康的年轻不吸烟男性在5周内接受以下药物或药物组合：第1周）美托洛尔；第2周）甲苯磺丁脲；第3周）咖啡因、氯唑沙宗和氨苯砜；第4周）咖啡因、氯唑沙宗、氨苯砜和美托洛尔；第5周）咖啡因、氯唑沙宗、氨苯砜、美托洛尔和甲苯磺丁脲。这些药物在睡前自行服用，并在接下来的8小时收集尿液。
单独给予美托洛尔（平均变化 - 11%）或甲苯磺丁脲（平均变化 - 0.3%）后获得的平均摩尔表型比率，与同时给予其他药物时获得的比率无显著差异（P > 0.05）。CYP3A4、CYP2D6、CYP2C9、CYP2E1、CYP1A2、N - 乙酰转移酶2和黄嘌呤氧化酶代谢比率的受试者内平均变异系数分别为33%、18%、22%、13%、16%、13%和5%。在同时给予五种探针药物的各种组合期间未观察到显著相互作用（P > 0.5）。
我们提出，这种由五种广泛可得药物组成的鸡尾酒式组合，是在大量人群中同时测定主要CYP酶活性的一种有前景的方法。
