Horai Y, Nakano M, Ishizaki T, Ishikawa K, Zhou H H, Zhou B I, Liao C L, Zhang L M
Division of Clinical Pharmacology, National Medical Center, Tokyo, Japan.
Clin Pharmacol Ther. 1989 Aug;46(2):198-207. doi: 10.1038/clpt.1989.126.
We examined genetically determined oxidation polymorphisms of metoprolol and mephenytoin in 200 unrelated, healthy Japanese subjects and in 98 mainland Chinese subjects simultaneously. This examination was done according to the respective reported phenotyping criteria by use of the urinary metabolic ratio of metoprolol and of the percentage of excretion of 4-hydroxymephenytoin 8 hours after dose administration. The frequencies of occurrence of poor metabolizers (PMs) in the Japanese versus the Chinese subjects were 0.5% versus 0% for metoprolol and 22.5% versus 17.4% for mephenytoin, respectively. There were no statistically significant differences in these frequencies between the two Oriental populations. However, Chinese extensive metabolizers (EMs) showed a significantly lower excretion of alpha-hydroxymetoprolol (p less than 0.01) and 4-hydroxymephenytoin (p less than 0.001) than that of Japanese EMs, and the mode of the distribution histogram of the Chinese EMs for the two test probes was skewed compared with that of the Japanese EMs. The findings indicate that the two Far Eastern Oriental subject groups have a lower frequency of PM phenotype of debrisoquin/sparteine-type oxidation and a greater incidence of PM phenotype of mephenytoin oxidation compared with the respective frequencies reported from white subjects. However, the explanation for the observation that the metabolic capacities of the test drugs differed between the EMs of the two populations who had a similar ethnic origin and who resided in the same geographic area remains obscure.
我们同时对200名无亲缘关系的健康日本受试者和98名中国大陆受试者进行了美托洛尔和甲妥英基因决定的氧化多态性检测。检测是根据各自报道的表型标准，通过使用美托洛尔的尿代谢率以及给药8小时后4 - 羟基甲妥英的排泄百分比来进行的。日本受试者与中国受试者中慢代谢者（PMs）的出现频率，美托洛尔分别为0.5%和0%，甲妥英分别为22.5%和17.4%。这两个东方人群在这些频率上没有统计学上的显著差异。然而，中国的快代谢者（EMs）与日本的快代谢者相比，α - 羟基美托洛尔（p < 0.01）和4 - 羟基甲妥英（p < 0.001）的排泄显著更低，并且中国快代谢者针对这两种测试探针的分布直方图模式与日本快代谢者相比存在偏差。研究结果表明，与白人受试者报告的各自频率相比，这两个远东东方受试者群体中去甲异喹胍/鹰爪豆碱型氧化的PM表型频率较低，而甲妥英氧化的PM表型发生率较高。然而，对于两个具有相似种族起源且居住在同一地理区域的人群的快代谢者之间测试药物代谢能力存在差异这一观察结果的解释仍然不清楚。
