USE OF MEASUREMENTS OF ETHANOL ABSORPTION FROM STOMACH AND INTESTINE TO ASSESS HUMAN ETHANOL-METABOLISM

Controversy exists concerning the site (stomach vs. liver) and magnitu de of first-pass metabolism of ethanol. We quantitated gastric and tot al ethanol absorption rates in five male subjects and utilized these m easurements to evaluate first-pass metabolism. Gastric emptying of eth anol (0.15 g/kg) was determined via a gamma camera and gastric absorpt ion from the ratio of gastric ethanol to [C-14]polyethylene glycol. Ga stric absorption accounted for 30% and 10% of ethanol administered wit h food and water, respectively. With food, estimated gastric mucosal e thanol concentrations fell from 19 to 5 mM over 2 h. Calculations usin g these concentrations and kinetic data for gastric alcohol dehydrogen ase showed <2% of the dose underwent gastric metabolism. Application o f observed ethanol absorption rates to a model of human hepatic ethano l metabolism indicated that only 30% and 4% of the dose underwent firs t-pass metabolism when administered with food and water, respectively. We conclude that virtually all first-pass ethanol metabolism occurs i n the liver and first-pass metabolism accounts for only a small fracti on of total clearance.