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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，有很多潮红者在饮酒时出现潮红反应，这是因为乙醛脱氢酶（ALDH2）活性部分缺陷导致乙醛蓄积。我们检查了使用和不使用氰胺治疗（ALDH2 抑制剂）时血液乙醇水平对乙醛和乙酸盐处置的影响。使用了兔子。将乙醇盐水溶液以1.0或2.0g/kgBW静脉内给予这些兔子20分钟，然后恒速输注(0.25g/kg/hr)。在第4小时和第8小时，输注速率增加至0.5g/kg/小时，持续1小时。通过顶空气相色谱法测量血液乙醇、乙醛和乙酸浓度。我们发现血液中乙醇浓度在2小时内达到稳定状态。血液乙醛浓度随着血液乙醇水平的增加而呈现尖峰状增加，在增加后约1小时达到稳定状态。浓度变化与血液乙醇浓度成正比，表明乙醛毒性可能随乙醇量的增加而增加。我们还发现血液醋酸盐浓度在给药后 2 小时内达到稳定状态。氰胺处理导致血液乙醛升高。乙酸盐水平恒定，其分布几乎不受血液乙醇水平增加的影响。我们的结果表明乙醛的动力学性质与乙酸不同