H-2 ANTAGONISTS AND ALCOHOL - DO THEY INTERACT

There are conflicting data on the existence of significant first-pass metabolism of alcohol (ethanol) in the human stomach and its inhibitio n by histamine H-2-receptor antagonists. Alcohol is predominandy metab olised in the liver by the microsomal alcohol oxidising system, alcoho l dehydrogenase (ADH) and a catalase enzyme. Histochemical and kinetic studies have revealed several ADH isoenzymes in the gastric mucosa wi th different kinetic properties. After small oral doses of alcohol fir st-pass metabolism in the stomach occurs, as shown by reduced area und er the plasma concentration-time curve (AUC) compared with intravenous or intraduodenal administration. The activity of gastric ADH is reduc ed in women, the elderly, Asian individuals, the fasting state, chroni c alcoholism and after gastrectomy. The effect is only present with sm all (less-than-or-equal-to 0.3 g/kg) alcohol doses and with a high alc ohol concentration. In a number of studies, cimetidine in therapeutic doses over 7 days produced a significant increase in the AUC and in th e peak plasma concentration after administration of alcohol 0. 15 and 0.30 g/kg. This was related to an inhibition of gastric ADH activity, as shown by in vitro studies. Ranitidine inhibited gastric ADH to a si milar extent on a molar basis, but its effect on alcohol levels in viv o was less constant in various studies. Nizatidine also reduced gastri c alcohol first-pass metabolism, but famotidine and roxatidine did not show this effect. In other studies, H-2-receptor antagonists did not change AUC and peak alcohol concentration. The controversy is not easy to resolve, since a number of the positive studies did not use a Plac ebo-controlled, randomised, crossover design, while some of the negati ve studies did not exclude habitual alcohol consumers and included Ori ental volunteers, although both groups have been shown to lack signifi cant gastric ADH activity. In this case, when first-pass metabolism of alcohol does not exist, this by definition cannot be abolished by H-2 -antagonists. The inclusion of oral and intravenous dosage data of alc ohol is mandatory to positively identify first-pass metabolism in any individuals. The significance of the effect of H-2-antagonists on bloo d alcohol concentrations is minor. It only occur, in young, male, nona lcoholic, non-Asian individuals and alcohol must be given in a small ( social) dose, in a high concentration, and after meals. An increase in alcohol levels in predisposed patients during treatment with some H-2 -antagonists cannot be excluded, although the likelihood is small. Fur thermore, carefully designed studies are needed to clarify fully the s ignificance of this interaction.