Ethanol pharmacokinetics in healthy man: Michaelis-Menten parameters and the circadian rhythm

Eleven presumed healthy subjects ingested in random order 3 different doses of ethanol (0.4, 0.6, 0.8 g X kg body weight-1) at 4 different times of day (0600, 1200, 1800, 0000). The rates of ethanol metabolism were measured by calculating the rate of decline of the linear portion of a plot of urinary concentration of ethanol against time (making correction for the ratio of ethanol in blood and urine). The rate of metabolism depended upon the dose of ethanol ingested and the peak concentration of urinary ethanol. The results lend further support to the view that the metabolic removal of ethanol can be described by Michaelis-Menten kinetics. Estimates of the Michaelis-Menten parameters Km and Vmax were made by considering the curvilinear portion of the decay curve at low concentrations. The values of these varied with time of ethanol ingestion; in particular, variation in Vmax can substantially account for the circadian rhythm of ethanol metabolism that had been measured previously.