Hou Z Y, Pickle L W, Meyer P S, Woosley R L
Department of Pharmacology, Georgetown University School of Medicine, Washington DC 20007.
Clin Pharmacol Ther. 1991 Apr;49(4):410-9. doi: 10.1038/clpt.1991.48.
Debrisoquin oxidative phenotype is a determinant of pharmacologic response for many drugs. Poor and extensive metabolizers can be identified by the dextromethorphan metabolic ratio (dextromethorphan/dextrorphan). We developed and tested a method to determine debrisoquin phenotype on the basis of the metabolic ratio in saliva. Each of 62 normal volunteers was given a 50 mg capsule of dextromethorphan hydrobromide and collected urine (0 to 8 hours) and saliva (at 3 hours). Dextromethorphan and dextrorphan in saliva and urine were assayed by HPLC. The distributions of paired urinary and 3-hour salivary metabolic ratios of samples from 61 subjects were compared. The urinary and salivary metabolic ratios were distributed trimodally and bimodally, respectively. The Spearman rank correlation coefficient for logarithm of urinary metabolic ratio vs that of salivary metabolic ratio was 0.704. All the poor metabolizers identified by urinary metabolic ratio were also identified by the metabolic ratio in saliva at 3 hours (100% concordance). This study demonstrates that salivary analysis for determination of dextromethorphan metabolic phenotype is feasible.
异喹胍氧化表型是许多药物药理反应的一个决定因素。弱代谢者和强代谢者可通过右美沙芬代谢率(右美沙芬/右啡烷)来识别。我们开发并测试了一种基于唾液中代谢率来确定异喹胍表型的方法。62名正常志愿者每人服用一粒50毫克的氢溴酸右美沙芬胶囊,并收集尿液(0至8小时)和唾液(3小时时)。通过高效液相色谱法测定唾液和尿液中的右美沙芬和右啡烷。比较了61名受试者样本的配对尿液和3小时唾液代谢率的分布情况。尿液和唾液代谢率分别呈三峰分布和双峰分布。尿液代谢率对数与唾液代谢率对数的Spearman等级相关系数为0.704。所有通过尿液代谢率鉴定出的弱代谢者也可通过3小时时唾液中的代谢率鉴定出来(一致性为100%)。这项研究表明,通过唾液分析来确定右美沙芬代谢表型是可行的。