Streetman D S, Ellis R E, Nafziger A N, Leeder J S, Gaedigk A, Gotschall R, Kearns G L, Bertino J S
Clinical Pharmacology Research Center, the Department of Medicine, Bassett Healthcare, Cooperstown, NY 13326-1394, USA.
Clin Pharmacol Ther. 1999 Nov;66(5):535-41. doi: 10.1016/S0009-9236(99)70018-4.
Most dextromethorphan CYP2D6 phenotyping studies use a 30-mg dose, but data that show superiority of any particular dose are lacking. We compared metabolic ratios from six different dextromethorphan phenotyping doses to ascertain whether linearity existed over a dosage range. Forty subjects were enrolled in the study. Each subject received 0.05 mg/kg, 0.15 mg/kg, 0.3 mg/kg, 30 mg, 0.8 mg/kg, and 1.2 mg/kg dextromethorphan in a randomized crossover fashion. Urinary dextromethorphan to dextrorphan molar ratios were used to measure CYP2D6 activity. Single blood samples were obtained for CYP2D6 genotyping, which revealed one poor metabolizer and 39 extensive metabolizers. A statistical difference was found for the molar ratio between the 0.8 mg/kg and the 1.2 mg/kg dose compared with the other four doses. None of the 39 genotypic extensive metabolizers were incorrectly phenotyped with any of these doses. These data support the use of moderate doses of dextromethorphan for phenotyping to avoid dose dependency.
大多数右美沙芬CYP2D6表型研究使用30毫克剂量，但缺乏表明任何特定剂量更具优势的数据。我们比较了六种不同右美沙芬表型剂量的代谢率，以确定在一个剂量范围内是否存在线性关系。40名受试者参与了该研究。每位受试者以随机交叉方式接受0.05毫克/千克、0.15毫克/千克、0.3毫克/千克、30毫克、0.8毫克/千克和1.2毫克/千克的右美沙芬。尿中右美沙芬与右啡烷的摩尔比用于测量CYP2D6活性。采集单份血样进行CYP2D6基因分型，结果显示有1名代谢不良者和39名代谢正常者。与其他四个剂量相比，0.8毫克/千克和1.2毫克/千克剂量之间的摩尔比存在统计学差异。39名基因分型代谢正常者中，没有一人因这些剂量中的任何一种而被错误地表型。这些数据支持使用中等剂量的右美沙芬进行表型分析，以避免剂量依赖性。
