ABSTRACT
Ethanol (also referred to as alcohol in this chapter) is probably the most widely investigated drug in the world, not only because of its ubiquitous use and its widespread abuse, but also because of its unique pharmacological properties. Following administration, systemic concentrations of alcohol are a consequence of the absorption
and metabolism of alcohol, which display unique characteristics and demonstrate substantial interindividual variability.1 As the pharmacological effects of alcohol depend on its systemic concentrations, variability in the pharmacokinetics of alcohol can have a significant impact on its pharmacodynamic effects. Following oral ingestion, alcohol is absorbed by passive diffusion, primarily from the small intestine.2,3 The rate of absorption depends on several factors, both genetic and environmental, and is highly variable.1 Some of these factors include the volume, concentration and nature of the alcoholic beverage,2,4,5 the rate of drinking,4 the fed or fasted state,6 the nature and composition of food,6,7 rate of gastric emptying,8,9 gender differences in first-pass metabolism,10,11 and other drugs including histamine (H1) receptor antagonists like cimetidine and ranitidine.12,13 Ethanolisa small polar molecule and its volume of distribution is comparable to total body water.3 No plasma protein binding has been reported for alcohol. Elimination of alcohol occurs primarily through metabolism with small fractions of the administered dose being excreted in the breath (0.7%), sweat (0.1%), and urine (0.3%).3 Alcohol metabolism occurs mainly via hepatic oxidation and is governed by the catalytic properties of the alcohol metabolizing enzymes, alcohol dehydrogenase (ADH), and aldehyde dehydrogenase (ALDH). The cytochrome P450 enzymes (CYP2E1) and catalase also contribute to alcohol metabolism and alcohol-related cytotoxicity in specific circumstances.14
