Effects of fasting and chronic alcohol consumption on the first-pass metabolism of ethanol

The present investigation was undertaken to evaluate what fraction of alcohol ingested in amounts during usual "social drinking" does not enter the systemic circulation. To that effect, on consecutive days, either peroral or intravenous ethanol was administered in both fed and fasted states to 7 nonalcoholic and 18 alcoholic subjects. In nonalcoholics consuming 0.15 g/kg body wt ethanol, the magnitude of first-pass metabolism of ethanol was 3.94 +/- 0.15 mmol/L X h, calculated as the difference of the areas under the curve obtained after oral and intravenous alcohol administration. The first-pass metabolism accounted for 73% of the latter. When the administered dose was increased to 0.3 g/kg body wt ethanol, the corresponding values were 6.46 +/- 0.50 mmol/L X h and 44%. Fasting decreased this effect. When alcoholics consumed 0.15 g/kg body wt ethanol, the corresponding values were 0.92 +/- 0.65 mmol/L X h and 23%. When these alcoholics were fasted, the first-pass metabolism again decreased and it was significantly lower than in the nonalcoholics tested under the same conditions. We conclude that in humans a significant fraction of ingested alcohol undergoes first-pass metabolism but that this effect is reduced in alcoholics and by fasting. The magnitude of this process determines the bioavailability of alcohol and thus modulates its potential toxicity.