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Pharmacokinetic Studies on Alcohol, Acetaldehyde and Acetate ; Their Relationship to Organ Damage

酒精、乙醛和乙酸的药代动力学研究；

基本信息

批准号：
09670447
负责人：
FUJIMIYA Tatsuya
金额：
$ 1.34万
依托单位：
Kyoto Prefectural University of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09670447/
关键词：
Alcohol Pharmacokinetics Acetaldehyde Acetate Alcoholic Organ damage Michaelis-Menten kinetics 過酸化脂質

项目摘要

Alcohol is metabolized and changed to acetaldehyde and acetic acid. The effects of acetate on organ damages have hardly been studied. This research aimed at studying the pharmacokinetic properties of ethanol, acetaldehyde and acetate, and relationships between their kinetic properties and organ damages. The animal experiments using rabbits were carried out. The blood ethanol, acetaldehyde and acetate concentrations were measured by gas chromatography (Shimadzu headspace gas chromatograph analysis system : GC-9A, HSS-2A, and C-R4A). Blood acetaldehyde concentration was measured by the perchrolic acid (PCA) method. Blood acetate concentration was measured by the method of Gilles et al. Plasma lipidperoxide, LDH and GPT levels were also measured using spectrophotometoric method (Shimadzu : UVl600) as indexes of organ damages. As a result, the increases of these levels were seen. However, their tendencies were irregular due to individual differences of responses. Consequently, further study seems to be needed. On the other hand, the clearance of alcohol is not constant because of its nonlinear-kinetic nature. Therefore, it is difficult to study the kinetic of alcohol, acetaldehyde and acetate and simultaneous multi-lines fitting should be adopted. We conducted moment analysis using blood alcohol, acetaldehyde and acetate profiles. As a result, the blood acetaldehyde concentration-time curve shows 2 peaks-pattern and the 2nd peak seems to correspond to its metabolic formation through the liver. The blood acetate disappearance curve showed non-linear natures. Simultaneous multi-lines curve- fitting using blood disappearance curves of alcohol and acetate was applied. As a result, the disappearance of blood alcohol and acetate revealed to obey Michaelis- Menten elimination kinetics.

酒精被代谢并转化为乙醛和乙酸。醋酸盐对器官损伤的影响几乎没有研究。本研究旨在研究乙醇、乙醛和乙酸的药代动力学特性及其与器官损伤的关系。采用家兔进行动物实验。通过气相色谱法（Shimadzu顶空气相色谱分析系统：GC-9A、HSS-2A和C-R4 A）测量血液乙醇、乙醛和乙酸盐浓度。用高氯酸（PCA）法测定血液乙醛浓度。采用Gilles等的方法测定血中醋酸盐浓度，并采用紫外线分光光度法（Shimadzu：UV 1600）测定血浆过氧化脂质、乳酸脱氢酶（LDH）和谷丙转氨酶（GPT）水平，作为脏器损伤的指标。因此，这些水平有所增加。然而，由于个体反应的差异，他们的趋势是不规则的。因此，似乎需要进一步研究。另一方面，由于其非线性动力学性质，酒精的清除率不是恒定的。因此，乙醇、乙醛和乙酸的动力学研究比较困难，应采用多线同时拟合的方法。我们使用血液中的酒精、乙醛和乙酸盐谱进行矩分析。结果，血液乙醛浓度-时间曲线显示2个峰型，第2个峰似乎对应于其通过肝脏的代谢形成。血醋酸盐消失曲线呈非线性。同时使用乙醇和乙酸的血液消失曲线进行多线曲线拟合。结果表明，血中乙醇和乙酸根的消失符合米氏消除动力学规律.