H2-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 inhibition by histamine H2-receptor antagonists. Alcohol is predominantly metabolised in the liver by the microsomal alcohol oxidising system, alcohol dehydrogenase (ADH) and a catalase enzyme. Histochemical and kinetic studies have revealed several ADH isoenzymes in the gastric mucosa with different kinetic properties. After small oral doses of alcohol first-pass metabolism in the stomach occurs, as shown by reduced area under the plasma concentration-time curve (AUC) compared with intravenous or intraduodenal administration. The activity of gastric ADH is reduced in women, the elderly, Asian individuals, the fasting state, chronic alcoholism and after gastrectomy. The effect is only present with small (< or = 0.3 g/kg) alcohol doses and with a high alcohol concentration. In a number of studies, cimetidine in therapeutic doses over 7 days produced a significant increase in the AUC and in the 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 similar extent on a molar basis, but its effect on alcohol levels in vivo was less constant in various studies. Nizatidine also reduced gastric alcohol first-pass metabolism, but famotidine and roxatidine did not show this effect. In other studies, H2-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 placebo-controlled, randomised, crossover design, while some of the negative studies did not exclude habitual alcohol consumers and included Oriental volunteers, although both groups have been shown to lack significant gastric ADH activity. In this case, when first-pass metabolism of alcohol does not exist, this by definition cannot be abolished by H2-antagonists. The inclusion of oral and intravenous dosage data of alcohol is mandatory to positively identify first-pass metabolism in any individuals. The significance of the effect of H2-antagonists on blood alcohol concentrations is minor. It only occurs in young, male, nonalcoholic, 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 H2-antagonists cannot be excluded, although the likelihood is small. Furthermore, carefully designed studies are needed to clarify fully the significance of this interaction.

RCT Entities:   Population Interventions Outcomes