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

酒精被代谢并转化为乙醛和醋酸。本研究旨在研究乙醛和乙酸乙酯在乙醇氧化过程中的药代动力学特性。研究了葡萄糖和果糖预处理对乙醛和乙酸乙酯降解的影响。用兔进行动物实验。我们初步给予葡萄糖和果糖来改善乙醇代谢。采用岛津顶空气相色谱分析系统GC-14B、HSS-2B和C-R7Aplus测定血液中乙醇、乙醛和乙酸乙酯浓度。全铬酸法测定血乙醛浓度。用Gilles等人的方法测定血醋酸酯浓度。结果表明，果糖和葡萄糖的预处理改善了乙醛、乙酸乙酯和乙醇的代谢。我们用血液中的酒精、乙醛和醋酸盐进行了力矩分析。因此，乙醛血药浓度-时间曲线呈双峰型，第二个峰似乎与其通过肝脏的代谢形成相对应。血乙醛消失率曲线和力矩分析结果均呈非线性。用乙醇和乙醛的血消失率曲线同时进行多直线拟合。结果表明，血液中乙醇和乙醛的消失符合米氏消除动力学。

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.