中国壮族志愿者S─美芬妥英和异喹胍羟化代谢多态性研究

Hydroxylation Polymorphisms of S─mephenytoin aDebrisoquin in Native Normal Chinese Zhuang MinorityVolunteers

１１８名中国壮族（广西壮族自治区）志愿者一次口服消旋美芬妥英１００ｍｇ和异喹胍１０ｍｇ后，应用气相色谱法分别测定尿中Ｓ─和Ｒ─美芬妥英含量比值和异喹胍及其代谢物４羟异喹胍含量比值，作为体内药物羟化代谢能力的指标。实验结果表明，１１８名志愿者中有１２名的Ｓ／Ｒ美芬妥英比值大于１．０，是为Ｓ─美芬妥英弱羟化代谢者。说明我国壮族人群中Ｓ─美芬妥英羟化代谢缺陷频发率高达１０．２％。但在１１８名壮族志愿者中未发现异喹胍弱羟化代谢者，且Ｓ─美芬妥英的羟化代谢多态性和异喹胍羟化代谢多态性不存在着相关性。另外，选择其中１６名志愿者（４名弱代谢者，１２名强代谢者）研究了尿中美芬妥英和异喹胍及其代谢物的消除动力学规律。并估算了它们主要的药代动力学参数。

S ─mephenytoin and debrisoquin hydroxylation abilities were investigated in 118 normal Chinese Zhuang minority volunteers after co─administration po 100 mg racemic mephenytoin(MP)and 10 mg debrisoquin (DB). The ratio between S─and R─enantiomers of mephenytoin in urinewas determined by implication of GC─NPD and used as the measure of the drug hydroxylation. 2 ofthe 118 subjects had S/R ratios greater than 1.0 and were poor hydroxylators of S─ mephenytoin. The frequency of S─mephenytoin poor metabolizers (PM) was 10.2%. No PM of debrisoquin was found in the volunteers. It indicated that there was no relationship between S─mephenytoin P(4 ′)─ hydroxylation and debrisoquin 4─hydroxylation polymorphisms in Chinese Zhuang Minority population. In addition, 16 of the 118 volunteers(4 PMs and 12 EMs of S-mephenytoin) were se─lected to conduct the elimination kinetic studies of racemic mephenytoin and debrisoquin in urine. The pharmacokinetic parameters of S─, R─ mephenytoin, DB and 4─OH─DB were calculated.