我国正常志愿者S-美芬妥英(Mephenytoin)羟化代谢缺陷频发率及其与异喹胍羟化代谢表型的相关性研究  

S-MEPHENYTOIN HYDROXYLATION POLYMORPHISM AND ITS RELATION TO DEBRISOQUINE HYDROXYLATION PHENOTYPE IN NATIVE NORMAL CHINESE SUBJECTS

作　　者：楼雅卿[1] L.Bertilsson 杜云龙[1] F.Sjoqvist 

机构地区：[1]北京医科大学药理教研室,北京100083 [2]Department of clinical Pharmacology, Huddinge University Hospital, Sweden

出　　处：《中国临床药理学杂志》1992年第1期32-36,共5页The Chinese Journal of Clinical Pharmacology

基　　金：国家级自然科学基金;编号852672生8548;卫生部科学研究基金;编号88314242

摘　　要：应用气相色谱法测定我国137名正常志愿者一次口服美芬妥英(100mg)和异喹胍(10mg)尿样中S/R美芬妥英比值和异喹胍/4-羟异喹胍比值。研究结果表明,137名志愿者中有20名为S-美芬妥英羟化代谢的弱代谢者(PMs),其缺陷频发率为14.6%,说明我国人群的S-美芬妥英羟化代谢缺陷频发率与日本人相近,但明显高于白种人。研究结果尚发现,137名志愿者有2例为异喹胍羟化代谢弱代谢者,其缺陷频发率为1.46%,并与S-美芬妥英羟化代谢表型不相关。这说明两药虽在体内均进行4-羟化代谢,但却被不同的细胞色素P_(450)羟化酶所催化和受不同酶基因所调控。Mephenytoin (100mg) and debrisoquine (10mg) were coadministered orally. Theratio between the S- and R- enantiomers of mephenytoin and the ration between debrisoquine and 4- hydroxyldebrisouine (metabolic ratio, MR) in 8 h urine were determined by gas chromatography withNPD or PID respectively. These ratios were used as measures of drug hydroxylation capacity. In the137 native normal Chinese subjects the frequency of PMs of s-mephenytoin hydroxylation was foundto be 14.6% (20/137) which is similar to the previously reported results in Japanese population (18-22%), but much higher than that in the Caucasian populations (2.4-5.4%). Thus, we can concludethat there are pronounced differences in the incidence of S-mephenytoin hydroxylation of PMs betweenOriental and Caucasian populations. Our results also showed that there was no relationship between S-mephenytoin and debrisoquine hydroxylation phenotypes in 137 native Chinese subjects. These dis-parate findings demonstrated that the S-mephenytoin and debrisoquine hydroxylases are two differentisozymes of the cytochrome P_(450) family and the independence of two oxidative metabolizing traits.

关 键 词：S-美芬妥英 异喹胍 羟化代谢 

分 类 号：R968[医药卫生—药理学]