Fundamental study on the estimation of blood concentration of ethanol and its metabolites

乙醇及其代谢物血药浓度估算的基础研究

基本信息

批准号：
14570388
负责人：
FUJIMIYA Tatsuya
金额：
$ 2.24万
依托单位：
Yamaguchi University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570388/
关键词：
Alcohol Acetaldehyde Acetate Pharmacokinetics Toxicokinetics Drug kinetics Metabolite Individual difference DNA多型

项目摘要

In Japan, there are many flushers who have flushing reactions during alcohol drinking, since they accumulate acetaldehyde due to partial defect of activity of aldehyde dehydrogeuase (ALDH2). We examined the effects of blood ethanol level on the disposition of acetaldehyde and acetate with and without cyanamide treatment, which is the inhibitor of ALDH2. Rabbits were used. An ethanol saline solution was administered intravenously into these rabbits at 1.0 or 2.0 g/kgBW for 20 minutes, followed by constant-rate infusion (0.25 g/kg/hr). At 4 and 8hr, the infusion rate was increased to 0.5 g/kg/hr for 1 hr. Blood ethanol, acetaldehyde and acetate concentrations were measured by headspace gas chromatography. We found that blood ethanol concentration reaches a steady state within 2 hours. The blood acetaldehyde concentration exhibited a spike-like increase in response to increases in the blood ethanol level, reaching a steady state around 1 hr after the increase. The change in concentration was in proportion to blood ethanol concentration, suggesting that acetaldehyde toxicity may increase with ethanol amount. We also found that blood acetate concentration reaches a steady state within 2 hr of administration. Blood acetaldehyde increased by the cyanamide treatment. The acetate level was constant, and its profile was hardly influenced by increases in the blood ethanol level. Our results indicate that the kinetic nature of acetaldehyde is different to that of acetate

在日本，有许多冲洗器在饮酒期间有潮红反应，因为由于醛脱氢过程的部分缺陷，它们会积累乙醛（Aldh2）。我们检查了血液乙醇水平对乙醛和乙酸酯对有或没有氰胺处理的处理的影响，这是ALDH2的抑制剂。使用兔子。将乙醇盐溶液以1.0或2.0 g/kgbw的静脉内静脉内施用20分钟，然后进行恒定速率输注（0.25 g/kg/hr）。在4和8小时时，输注率增加到0.5 g/kg/hr 1小时。通过顶空气相色谱法测量血液乙醇，乙醛和乙酸盐浓度。我们发现血液乙醇浓度在2小时内达到稳态。血液乙醛浓度对血液乙醇水平升高的响应表现出类似尖峰的增加，在增加后达到1小时左右。浓度的变化与血液乙醇浓度成正比，表明乙醛毒性可能随乙醇量增加。我们还发现，乙酸血液浓度在给药2小时内达到稳态。血液乙醛通过氰酰胺治疗增加。乙酸水平是恒定的，其特征几乎不受血液乙醇水平的升高影响。我们的结果表明，乙醛的动力学性质与乙酸不同