DISPOSITION AND FIRST-PASS METABOLISM OF ETHANOL IN HUMANS - IS IT GASTRIC OR HEPATIC AND DOES IT DEPEND ON GENDER

Objective: To assess the extent and site of the first-pass metabolism of ethanol and to examine whether first-pass metabolism and dispositio n of ethanol are dependent on gender. Methods: After a standardized lu nch, healthy subjects (six women and six men) received on two separate occasions a 60-minute intravenous infusion of ethanol (0.3 gm/kg) and concomitantly an equimolar dose of d(3)-ethanol/kg either orally (ove r 20 minutes) or intraduodenally (infused over 30 minutes), Blood leve ls, urinary excretion of d(0)- and d(3)-ethanol, and sedative effects were monitored for 6 hours. Disposition and first-pass metabolism of e thanol were evaluated by applying an open two-compartment model with M ichaelis-Menten elimination. Results: Comparison of the corresponding intravenous/oral versus intravenous/intraduodenal data of each individ ual revealed that total first-pass metabolism (gastric plus hepatic) w as not pronounced in either males (9.1% +/- 4.0%; mean +/- SD) or fema les (8.4% +/- 3.1%) and that this first-pass metabolism was partly of gastric origin. Dose-corrected values for area under the blood concent ration-time curve were on average 28% higher (p < 0.0001) in the women than in the men. Mean total blood ethanol disappearance rate was high er (p < 0.001) in women (3.92 +/- 0.40 mmol/L . hr) than in men (3.19 +/- 0.48 mmol/L . hr). Renal clearance was gender-independent and negl igible, A linear relationship (p < 0.001) could be found between the b lood levels of ethanol and sedation index. Because the slope was steep er in women (1.04) than in men (0.42) a higher central nervous system sensitivity to the sedative effects of ethanol in women can be assumed . Conclusions: Under realistic life conditions (social drinking of mod erate doses of ethanol after a light lunch) only a minor, gender-indep endent first-pass metabolism is observed that is partly of gastric ori gin.