Jones A W
Department of Forensic Toxicology, National Board of Forensic Medicine, Linköping, Östergöland, Sweden.
Forensic Sci Rev. 2011 Jul;23(2):91-136.
A reliable method for the quantitative analysis of ethanol in microvolumes (50-100 μL) of blood became available in 1922, making it possible to investigate the absorption, distribution, metabolism, and excretion (ADME) of ethanol in healthy volunteers. The basic principles of ethanol pharmacokinetics were established in the 1930s, including the notion of zero-order elimination kinetics from blood and distribution of the absorbed dose into the total body water. The hepatic enzyme alcohol dehydrogenase (ADH) is primarily responsible for the oxidative metabolism of ethanol. This enzyme was purified and characterized in the early 1950s and shown to have a low Michaelis constant (km), being about ~0.1 g/L. Liver ADH is therefore saturated with substrate after the first couple of drinks and for all practical purposes the concentration-time (C-T) profiles of ethanol are a good approximation to zero-order kinetics. However, because of dose-dependent saturation kinetics, the entire postabsorptive declining part of the blood-alcohol concentration (BAC) curve looks more like a hockey stick rather than a straight line. A faster rate of ethanol elimination from blood in habituated individuals (alcoholics) is explained by participation of a high km microsomal enzyme (CYP2E1), which is inducible after a period of chronic heavy drinking. Owing to the combined influences of genetic and environmental factors, one expects a roughly threefold difference in elimination rates of ethanol from blood (0.1-0.3 g/L/h) between individuals. The volume of distribution (Vd) of ethanol, which depends on a person's age, gender, and proportion of fat to lean body mass, shows a twofold variation between individuals (0.4-0.8 L/kg). This forensic science review traces the development of forensic pharmacokinetics of ethanol from a historical perspective, followed by a discussion of important issues related to the disposition and fate of ethanol in the body, including (a) quantitative evaluation of blood-alcohol curves and the factors influencing the peak concentration in blood (Cmax) and the time of its occurrence (tmax), (b) biological variations in the ADME of ethanol, including the apparent volume of distribution (Vd or rho), the disappearance rate from blood (β or k0), and the disposal rate by the entire body in 1 h (B60), and (c) questions about ADME of ethanol often arising during the prosecuting of accused drunken drivers.
1922年出现了一种可靠的方法，可对微量（50 - 100微升）血液中的乙醇进行定量分析，这使得研究健康志愿者体内乙醇的吸收、分布、代谢和排泄（ADME）成为可能。乙醇药代动力学的基本原理在20世纪30年代得以确立，包括血液零级消除动力学的概念以及吸收剂量在全身水中的分布。肝酶乙醇脱氢酶（ADH）主要负责乙醇的氧化代谢。这种酶在20世纪50年代早期被纯化并进行了特性鉴定，其米氏常数（km）较低，约为0.1 g/L。因此，喝了头几杯酒之后，肝脏中的ADH就会被底物饱和，实际上，乙醇的浓度 - 时间（C - T）曲线非常近似于零级动力学。然而，由于存在剂量依赖性饱和动力学，血液酒精浓度（BAC）曲线在吸收后下降的整个部分看起来更像曲棍球棒，而不是一条直线。习惯饮酒者（酗酒者）血液中乙醇消除速度更快，这是因为一种高km微粒体酶（CYP2E1）参与其中，这种酶在长期大量饮酒一段时间后会被诱导产生。由于遗传和环境因素的综合影响，预计个体之间血液中乙醇消除速率会有大约三倍的差异（0.1 - 0.3 g/L/h）。乙醇的分布容积（Vd）取决于一个人的年龄、性别以及脂肪与瘦体重的比例，个体之间会有两倍的差异（0.4 - 0.8 L/kg）。这篇法医学综述从历史角度追溯了乙醇法医药代动力学的发展，随后讨论了与乙醇在体内的处置和归宿相关的重要问题，包括（a）血液酒精曲线的定量评估以及影响血液中峰值浓度（Cmax）及其出现时间（tmax）的因素，（b）乙醇ADME的生物学变异，包括表观分布容积（Vd或rho）、血液中的消失速率（β或k0）以及全身在1小时内的处置速率（B60），以及（c）在起诉被控醉酒驾车者时经常出现的关于乙醇ADME的问题。
