Simulation Studies on Ethanol Metabolism in Different Human Populations with a Physiological Pharmacokinetic Model

Abstract

A physiological pharmacokinetic model of ethanol metabolism was used to simulate ethanol metabolism in standard, fasted, human males of the white American, white European, black American, and Japanese populations. Gastric ethanol metabolism accounted for only 0.24% of the dose in the several populations. In contrast, hepatic first-pass ethanol metabolism accounted for 3.7–4.2% of the dose. Ethanol elimination by the lung and kidney accounted for 1.3–1.7% of the dose in the several populations. The black American population had a significantly higher maximum blood ethanol concentration and area under the blood ethanol concentration versus time curve than the other populations studied when either a single dose or multiple doses of ethanol were ingested. These increases were due to the presence of a considerable amount of the β3β3-alcohol dehydrogenase (ADH) isoenzyme, with a Michaelis constant of 34 mM in the black American population. The Japanese population, which has a relatively high proportion of the β2β2-ADH isozyme, metabolized ethanol somewhat more rapidly than the other populations, as previously noted.