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

Background and 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 [1-¹⁴C]ethanol, and the quantity of ethanol oxidized was measured by the production of [1- ¹⁴C]acetate. Results: Gastric cells cultured from men produced 7.3 ± 3.5 μmol acetate · 10⁶ cells ¹ · h^-1, which was more than that generated in cells from women (3.2 ± 0.6; P < 0.05). Acetate production was inhibited by 4-methylpyrazole (a class I 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.