Sohn D R, Kusaka M, Shin S G, Jang I J, Chiba K, Ishizaki T
Department of Pharmacology, College of Medicine, Gyeongsang National University, Chinju, Korea.
Ther Drug Monit. 1992 Jun;14(3):184-9. doi: 10.1097/00007691-199206000-00002.
We examined the utility of the postdose 3-h plasma metabolic ratio (MR) as a phenotyping method for assessing genetically determined debrisoquine-type oxidation polymorphism after an oral dose of 100 mg of metoprolol tartrate administered to 402 unrelated, healthy, and native East Asian (218 Korean and 184 Japanese) subjects. All of them were phenotyped simultaneously with the reported MR employing urine samples collected during an 8-h postdose period. In the two populations, the distribution histograms and probit plots of log10plasma MRs derived from the metoprolol/alpha-hydroxymetoprolol concentration values indicated a large gap between the extensive and poor metabolizers who were phenotyped by the reported criteria of the 8-h urinary MR. There were statistically significant (p less than 0.001) correlations (rs = 0.688 and 0.810, respectively) between the postdose urinary and plasma MRs in the Korean and Japanese populations. Two poor metabolizers (one each included in the two racial groups) identified according to the 8-h urinary MR gave the greatest plasma MRs (i.e., 549.7 among the Koreans and 150.0 among the Japanese). The results suggest that the one-point, postdose 3-h plasma MR is also useful for the phenotyping purpose of oxidation pharmacogenetic polymorphism of metoprolol, a widely prescribed beta-adrenoceptor blocking drug.
我们对402名无亲缘关系、健康的东亚本土受试者（218名韩国人和184名日本人）口服100 mg酒石酸美托洛尔后，采用给药后3小时血浆代谢比（MR）作为一种表型分析方法，来评估基因决定的异喹胍型氧化多态性的效用。所有受试者均在给药后8小时内收集尿液样本，同时采用报告的MR进行表型分析。在这两个人群中，由美托洛尔/α-羟基美托洛尔浓度值得出的log10血浆MR的分布直方图和概率图表明，根据8小时尿MR的报告标准进行表型分析的快代谢者和慢代谢者之间存在很大差距。在韩国人和日本人群中，给药后尿MR与血浆MR之间存在统计学显著相关性（p<0.001）（rs分别为0.688和0.810）。根据8小时尿MR确定的两名慢代谢者（两个种族群体各一名）的血浆MR最高（即韩国人为549.7，日本人为150.0）。结果表明，给药后3小时的单点血浆MR对于广泛使用的β-肾上腺素受体阻滞剂美托洛尔氧化药物遗传多态性的表型分析目的也很有用。
