METABOLISM OF ALCOHOL BY HUMAN GASTRIC CELLS - RELATION TO FIRST-PASSMETABOLISM

Background & Aims: The bioavailability of orally administered alcohol is incomplete, indicating first-pass metabolism, There is debate regar ding the site of first-pass metabolism and specifically whether the st omach has the metabolic capacity to account for first-pass metabolism, The aim of this study was to assess ethanol metabolism by human gastr ic 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 fr om men produced 7.3 +/- 3.5 mu mol acetate . 10(6) cells(-1). h(-1), w hich 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 az ide (a catalase inhibitor), Cimetidine (a gastric ADH inhibitor) reduc ed acetate production by as much as 59%, whereas ranitidine had no sig nificant effect, Conclusions, Human gastric cells metabolize sufficien t alcohol to account for the bulk of first-pass metabolism, At least t wo isozymes of gastric ADH contribute to this metabolism. Cimetidine, but not ranitidine, inhibits gastric alcohol metabolism in keeping wit h its inhibition of in vivo first-pass metabolism.