Metabolism of alcohol by human gastric cells: Relation to first-pass metabolism

Background & Aims: The bioavailability of orally administered alcohol is incomplete, indicating first-pass metabolism, There is debate regarding the site of first-pass metabolism and specifically whether the stomach has the metabolic capacity to account for first-pass metabolism, The aim of this study was to assess ethanol metabolism by human gastric mucosa cells in primary culture, Methods: Cells were incubated with [1-C-14]ethanol, and the quantity of ethanol oxidized was measured by the production of [1-C-14]acetate, Results: Gastric cells cultured from men produced 7.3 +/- 3.5 mu mol acetate . 10(6) cells(-1). h(-1), which was move than that generated in cells from women (3.2 +/- 0.6; P < 0.05), Acetate production was inhibited by 4-methylpyrazole (a class 1 alcohol dehydrogenase [ADH] inhibitor) and by m-nitrobenzaldehyde (a selective substrate for class IV ADH isoenzyme) but not by sodium azide (a catalase inhibitor), Cimetidine (a gastric ADH inhibitor) reduced acetate production by as much as 59%, whereas ranitidine had no significant effect, Conclusions, Human gastric cells metabolize sufficient alcohol to account for the bulk of first-pass metabolism, At least two isozymes of gastric ADH contribute to this metabolism. Cimetidine, but not ranitidine, inhibits gastric alcohol metabolism in keeping with its inhibition of in vivo first-pass metabolism.