权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Effect of aldehyde dehydrogenase deficiency of ethanol elimination after peroral of intravenous administrations

乙醛脱氢酶缺乏对口服或静脉给药后乙醇消除的影响

基本信息

批准号：
62480184
负责人：
MIZOI Yasuhiko
金额：
$ 3.52万
依托单位：
Kobe University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

项目摘要

Japanese healthy male volunteers were divided into two groups, i.e., a normal aldehyde dehydrogenase (ALPH) group with a low Km isozyme of ALDN and a deficient group.In Experiment I, the subjects received 0.1 and/or 0.4 g/kg doses of ethanol perorally and intravenously in different days. After a light meal. 0.1 g/kg dose of ethanol was administered as well as the former. At the dose of 0.4 g/kg, the blood ethanol curve became pseudolinear and followed curvilinear. No marked difference was noted in the elimination rate between in the both administrations, and the decreases of the areas under the curve (AUC) were 13 % and 22 % in subjects with the normal and deficient ALDH, respectively. At the dose of 0.1 g/kg, the blood ethanol curve became curvilinear after reaching a peak value. The decreases of the AUC were 35 % and 33 %, respectively. High blood acetaldehyde levels over 10 M were observed only in the deficient subjects. After a meal, blood ethanol levels became low and the AUC decreased conspicuously in peroral administration. The differences in the AUC between peroral and intravenous administrations were apparent when a lower dose of ethanol was used. The proportion of the first pass effect in the ethanol metabolism is relatively low. After a meal, a delay of absorption and a decrease in its efficiency lead to the low ethanol levels and the decrease of the AUC.In Experiment II , 0.1 g/kg of ethanol was infused into the other twelve subjects. Ethanol elimination curves were fitted to the one compartment open nodel utilizing Michaelis-Menten elimination kinetics. The peak levels of the blood ethanol varied from 2.8 to 9.4 mM among the subjects. Apparent Km and Vmax values differed individually, the rate and volume of diffusion are also important factors in ethanol elimination.

日本健康男性志愿者分为两组，即ALDN Km低的正常乙醛脱氢酶(Alph)组和缺陷组。在实验I中，受试者在不同的时间分别口服和/或静脉注射0.1和/或0.4g/kg剂量的乙醇。在一顿清淡的饭后。对照组给予0.1g/kg乙醇灌胃。当剂量为0.4g/kg时，血液乙醇曲线变为伪直线，并遵循曲线。ALDH正常组和ALDH缺陷组的曲线下面积(AUC)分别减少13%和22%。当剂量为0.1g/kg时，血乙醇曲线在达到峰值后呈曲线变化。AUC分别下降35%和33%。血乙醛水平在10M以上者仅见于血乙醛缺乏者。餐后，口服给药组血中乙醇水平降低，AUC明显降低。当使用较低剂量的乙醇时，口服和静脉给药之间的AUC差异明显。首过效应在乙醇代谢中所占比例较低。在实验II中，其余12名受试者均按0.1g/kg的剂量注入乙醇。用Michaelis-Menten消除动力学拟合出乙醇消除曲线符合一室开放模型。受试者血液中乙醇的峰值浓度范围为2.8~9.4 mM。表观Km和Vmax值不同，扩散速率和扩散体积也是乙醇消除的重要因素。