In Vivo Interactions Between H2-Receptor Antagonists and Ethanol Metabolism in Man and in Rats

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Abstract
The influence of a 7-day medication of either cimetidine (1,000 mg per day) or ranitidine (300 mg per day) on serum ethanol concentrations after a single oral dose of ethanol (0.8 gm per kg body weight) was investigated in a randomized placebo-controlled study in eight male volunteers. Compared with the placebo, cimetidine but not ranitidine produced a significant increase in both the peak serum ethanol concentration (85.9 ± 3.5 vs. 73.0 ± 3.2 mg dl−1, p < 0.02) and in the area under the serum ethanol concentration time curve (350 ± 19 vs. 304 ± 25 mg dl−1hr−1, p < 0.05). However, the ethanol elimination rate was not affected by cimetidine. When ethanol (1.0 gm per kg body weight) was administered intravenously, cimetidine failed to induce a change in ethanol metabolism. Furthermore, the effect of H2-receptor antagonists was studied in animal experiments. Female Sprague-Dawley rats received a single dose of ethanol (7 or 3 gm per kg body weight) together with an intraperitoneal injection of either cimetidine (120 mg per kg body weight), ranitidine (120 mg per kg body weight) or isotonic saline. After alcohol absorption, ethanol elimination was significantly inhibited by both cimetidine (3.99 ± 0.39 vs. 5.68 ± 0.23 mmoles kg−1hr−1, p < 0.02) and ranitidine (4.21 ± 0.14 vs. 5.68 ± 0.23 mmoles kg−1hr−1, p < 0.02) at high ethanol concentrations (60 to 20 mM) but not at blood ethanol concentrations below 20 mM. These results suggest an increase in ethanol absorption due to cimetidine but not to ranitidine in man at ethanol serum concentrations below 20 mM. At ethanol serum concentrations above 20 mM, both H2-receptor antagonists inhibit ethanol elimination in the rat suggesting inhibition of microsomal ethanol oxidation.