Alcohol, its absorption, distribution, metabolism, and excretion in the body and pharmacokinetic calculations

The ethanol contained in alcoholic beverages is rapidly absorbed from the gastrointestinal tract and the maximum blood-alcohol concentration (BAC) is usually reached between 10 and 60 min postdosing. Once in the bloodstream, ethanol is distributed into the total body water (TBW) compartment, which comprises similar to 55-60% of body weight in nonobese males and similar to 50-55% in females. The volume of distribution (V-d) of ethanol depends on a person's age, gender, and degree of adiposity (ratio of fat to lean tissue). Studies have shown that the average Vd for healthy men and women are similar to 0.70 and similar to 0.60 L/kg, respectively. Elimination of ethanol from the body occurs primarily through metabolism (92-98% of dose) by hepatic alcohol dehydrogenase (ADH), an enzyme located in the liver cytosol and a microsomal enzyme, denoted CYP2E1. A small fraction (0.1-0.2%) of the dose of ethanol ingested undergoes nonoxidative metabolism by phase II conjugation reactions leading to formation of ethyl glucuronide and ethyl sulfate. Only between 2 and 10% of the dose of ethanol is excreted unchanged in urine, breath, and in sweat/perspiration. Ethanol exhibits dose-dependent pharmacokinetics, because the hepatic ADH enzyme is saturated with substrate at BAC above 15-20 mg/100 mL (15-20 mg%). Zero-order kinetics operate for most of the postabsorptive elimination phase and the BAC decreases at a constant rate per unit time ranging from 10 to 35 mg% per hour (average 15 mg% per hour for moderate drinkers). Examples of various pharmacokinetic calculations are presented because these are often necessary in forensic science and legal medicine casework. This article is categorized under: Toxicology > Alcohol Toxicology > Analytical Toxicology Toxicology > Drug-Impaired Driving