Interindividual variations in the disposition and metabolism of ethanol in healthy men

Abstract

Forty-eight healthy men each drank a dose of ethanol, 0.68 g/kg of body weight, as neat whisky at about 09.00, after fasting overnight. The drink was finished within 20 min and the concentrations of ethanol in samples of capillary blood were determined at 30–60 min intervals for 7 hr. Rectilinear regression lines were fitted to the elimination phase of blood concentration time profiles and blood-ethanol parameters were calculated as described by Widmark. In 23, 14, 8 and 3 subjects the peak blood ethanol concentrations were reached at 30, 60, 90 and 120 min timed from starting to drink. The highest concentration of ethanol in blood was 0.92±0.022 mg/ml (mean ±SE) and the coefficient of variation (CV) was 16.8%. The blood concentration of ethanol extrapolated to zero-time was 0.98±0.009 mg/ml (CV=6.5%) and the apparent volume of distribution (V d) was 0.695±0.0064 L/kg (CV=6.4%). The rate of ethanol elimination from blood was 0.126±0.0018 mg/ml/hr (CV=9.9%) and the body clearance was 87.5±1.1 mg/kg/hr (CV=8.7%). The apparent volume of distribution of ethanol was inversely related to the subject's body weight (r=−0.59±0.118, p<0.001). The elimination rate from blood was lower in those subjects with larger distribution volume; the parameters were negatively correlated (r=−0.52±0.126, p<0.001). The results show that blood-ethanol parameters calculated according to Widmark's method have low intersubject variability when the dose of ethanol administered and the condition of the test subjects are carefully controlled. A more sophisticated mathematical treatment of ethanol pharmacokinetics may be unnecessary.