Nagai N, Kawakubo T, Kaneko F, Ishii M, Shinohara R, Saito Y, Shimamura H, Ohnishi A, Ogata H
Department of Biopharmaceutics, Meiji College of Pharmacy, Tokyo, Japan.
Biopharm Drug Dispos. 1996 Jul;17(5):421-33. doi: 10.1002/(SICI)1099-081X(199607)17:5<421::AID-BDD421>3.0.CO;2-9.
The plasma concentration and cumulative urinary excretion over 34 h of dextromethorphan, free and conjugated dextrorphan, and 3-hydroxymorphinan were determined in seven healthy Japanese subjects after oral administration of 30 mg dextromethorphan hydrobromide. Conjugated metabolites were extensively present, whereas no detectable dextromethorphan or free metabolites were observed in the plasma of any subject. On average, 72% of the dose was excreted in urine within 34 h. This was detected mainly as conjugated metabolites with only slight traces of dextromethorphan and free metabolites. From the time-courses of the metabolic ratio (the ratio of urinary output of dextromethorphan to dextrorphan), the metabolic ratios seemed to become constant 7.5 h after oral administration. Phenotyping was performed using metabolic ratios in 75 unrelated healthy Japanese subjects (43 males and 32 females). The logarithmic metabolic ratio was bimodally distributed and one subject (1.3%) was identified as a poor metabolizer.
在7名健康日本受试者口服30mg氢溴酸右美沙芬后，测定了34小时内右美沙芬、游离和结合右啡烷以及3-羟基吗啡喃的血浆浓度和累积尿排泄量。结合代谢物广泛存在，而在任何受试者的血浆中均未观察到可检测到的右美沙芬或游离代谢物。平均而言，72%的剂量在34小时内随尿液排出。这主要检测为结合代谢物，仅含有微量的右美沙芬和游离代谢物。从代谢率（右美沙芬与右啡烷的尿排出量之比）的时间进程来看，口服给药7.5小时后代谢率似乎变得恒定。在75名无亲缘关系的健康日本受试者（43名男性和32名女性）中使用代谢率进行了表型分析。对数代谢率呈双峰分布，一名受试者（1.3%）被鉴定为代谢缓慢者。
