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.

将酒精代谢并改为乙醛和乙酸。这项研究旨在研究乙醇氧化过程中乙醛和乙酸酯的药代动力学特性。我们研究了葡萄糖和果糖预处理对乙醛和乙酸酯的处置的影响。使用兔子进行动物实验。我们初步施用葡萄糖和果糖来改善乙醇代谢。通过气相色谱法（Shimadzu Headspace气体色谱分析系统：GC-14B，HSS-2B和C-R7APLUS）测量血液乙醇，乙醛和乙酸盐浓度。通过高丙酸（PCA）方法测量血液乙醛浓度。通过Gilles等人的方法测量乙酸血液浓度。结果，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。我们使用血液酒精，乙醛和醋酸酯谱进行了力矩分析。因此，血液乙醛浓度曲线显示2个峰模式，第二个峰似乎与其通过肝脏的代谢形成相对应。血液乙醛消失曲线和力矩分析的结果显示出非线性的本质。使用酒精和乙醛的血液消失曲线同时进行多线曲线拟合。结果，血液酒精和乙醛的消失向服从Michaelis-Menten消除动力学。