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In Vivo Interactions Between H2‐Receptor Antagonists and Ethanol Metabolism in Man and in Rats
Author(s) -
Seitz Helmut K.,
Veith Siegrid,
Czygan Peter,
Bösche Johann,
Simon Bernd,
Gugler Roland,
Kommerell Burkhard
Publication year - 1984
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840040623
Subject(s) - in vivo , pharmacology , chemistry , metabolism , ethanol , medicine , endocrinology , biology , biochemistry , genetics
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 −1 hr −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 H 2 ‐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 −1 hr −1 , p < 0.02) and ranitidine (4.21 ± 0.14 vs. 5.68 ± 0.23 mmoles kg −1 hr −1 , p < 0.02) at high ethanol concentrations (60 to 20 m M ) but not at blood ethanol concentrations below 20 m M . These results suggest an increase in ethanol absorption due to cimetidine but not to ranitidine in man at ethanol serum concentrations below 20 m M . At ethanol serum concentrations above 20 m M , both H 2 ‐receptor antagonists inhibit ethanol elimination in the rat suggesting inhibition of microsomal ethanol oxidation.