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

酒精被代谢并转化为乙醛和醋酸。醋酸盐对器官损伤的影响几乎没有研究过。本研究旨在研究乙醇、乙醛和乙酸乙酯的药代动力学特性及其与器官损害的关系。用兔进行动物实验。采用岛津顶空气相色谱分析系统GC-9A、HSS-2A和C-R4A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。用分光光度法(岛津：UV1600)测定血浆过氧化脂质、乳酸脱氢酶和谷丙转氨酶水平，作为脏器损伤的指标。结果，这些水平出现了上升。然而，由于反应的个体差异，他们的倾向是不规则的。因此，似乎需要进一步的研究。另一方面，乙醇的清除量并不是恒定的，因为它具有非线性动力学性质。因此，乙醇、乙醛和乙酸乙酯的动力学研究比较困难，应采用多直线同时拟合的方法。我们用血液中的酒精、乙醛和醋酸盐进行了力矩分析。结果表明，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。血醋酸酯消失率曲线呈非线性。用乙醇和醋酸盐的血消失率曲线同时进行多直线拟合。结果表明，血液中乙醇和醋酸盐的消失符合米氏消除动力学。

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.