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Pharmacokinetic Studies on Alcohol and its Metabolites to Determine Their Kinetic Models

酒精及其代谢物的药代动力学研究以确定其动力学模型

基本信息

批准号：
12670400
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：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670400/
关键词：
Alcohol Acetaldehyde Acetate Pharmacokinetics Toxicokinetics Glucose Fructose Nutrition トキシコキネティクス

项目摘要

Alcohol is metabolized and changed to acetaldehyde and acetic acid. This research aimed at studying the pharmacokinetic properties of acetaldehyde and acetate during ethanol oxidation. We studied the effects of glucose and fructose pretreatments on disposition of acetaldehyde and acetate. The animal experiments using rabbits were carried out. We preliminarily administered glucose and fructose to improve ethanol metabolism. The blood ethanol, acetaldehyde and acetate concentrations were measured by gas chromatography ( Shimadzu headspace gas chromatograph analysis system: GC-14B, HSS-2B, and C-R7Aplus ). Blood acetaldehyde concentration was measured by the perchrolic acid ( PCA ) method. Blood acetate concentration was measured by the method of Gilles et al. As a result, the pretreatment of fructose and glucose improve the metabolism of acetaldehyde and acetate as well as ethanol. We conducted moment analysis using blood alcohol, acetaldehyde and acetate profiles. Consequently, 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 acetaldehyde disappearance curve and the results of moment analysis showed non-linear natures. Simultaneous multi-lines curve-fitting using blood disappearance curves of alcohol and acetaldehyde was applied. As a result, the disappearance of blood alcohol and acetaldehyde revealed to obey Michaelis-Menten elimination kinetics.

酒精被代谢并转化为乙醛和乙酸。本研究旨在研究乙醇氧化过程中乙醛和乙酸的药代动力学特性。研究了葡萄糖和果糖预处理对乙醛和乙酸盐降解的影响。采用家兔进行动物实验。我们初步给予葡萄糖和果糖以改善乙醇代谢。通过气相色谱法（Shimadzu顶空气相色谱分析系统：GC-14 B、HSS-2B和C-R7 Aplus）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等的方法测定血中乙酸浓度。结果表明，果糖和葡萄糖的预处理改善了乙醛和乙酸以及乙醇的代谢。我们使用血液中的酒精、乙醛和乙酸盐谱进行矩分析。因此，血液乙醛浓度-时间曲线显示2个峰模式，第2个峰似乎对应于其通过肝脏的代谢形成。血乙醛消失曲线及矩分析结果均呈非线性。同时使用酒精和乙醛的血液消失曲线进行多线曲线拟合。结果表明，血液中酒精和乙醛的消失符合米氏消除动力学。