First Pass Metabolism of Ethanol

The AUC is significantly lower after oral dosing of ethanol than after intravenous or intraperitoneal administration. The total dose of intravenously administered ethanol is available to the systemic circulation. The difference between AUCoral and AUCiv represents the fraction of the oral dose that was either not absorbed or metabolized before entering the systemic circulation (first-pass metabolism (FPM)). The ratio of AUCoral to AUCiv reflects the oral bioavailability of ethanol.

The investigation of ethanol metabolism has primarily focused on the liver and its relationship to liver pathology. However, gastric metabolism accounts for approximately 5% of ethanol oxidation and 2-10% is excreted in the breath, sweat, or urine. The rest is metabolized by the liver.

After absorption, ethanol is transported to the liver in the portal vein. Some is metabolized by the liver before reaching the systemic circulation. However, hepatic ADH is saturated at a BEC that may be achieved in an average-size adult after consumption of one or two units. If ADH is saturated by ethanol from the systemic blood via hepatic artery, ethanol in the portal blood must compete for binding to ADH. Although hepatic oxidation of ethanol cannot increase once ADH is saturated, gastric ADH can significantly metabolize ethanol at the high concentrations in the stomach after initial ingestion. If gastric emptying of ethanol is delayed, prolonged contact with gastric ADH increases FPM. Conversely, fasting, which greatly increases the speed of gastric emptying, virtually eliminates gastric FPM.

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