Effects of various concomitant medications on gastric alcohol dehydrogenase and the first-pass metabolism of ethanol.
Inhibition of gastric alcohol dehydrogenase (ADH) has been shown to enhance alcohol absorption in man under certain circumstances. To determine whether various medications might affect alcohol absorption, we screened 18 compounds for an effect on ADH. Salicylic acid, acetaminophen, propranolol, ethacrynic acid, and three H2-receptor antagonists all inhibited rat gastric ADH in vitro, indicating that several commonly used medications have the potential to enhance alcohol absorption. Of these, cimetidine, ranitidine, and nizatidine were studied further to define their effect on alcohol absorption in man and to assess the clinical relevance of the effect. Both ranitidine and nizatidine enhanced the absorption of small doses of alcohol (0.15 g/kg) in the morning by 63% and 64% and increased Cmax by 48% and 54% respectively (p less than 0.001), effects similar to those reported by others for cimetidine. The effect of ranitidine given before dinner was greatly attenuated with increases in Cmax of 8% (NS) and AUC of 21% (p = 0.02). Cimetidine 800 mg hs did not affect the absorption of 0.15 g/kg alcohol given in the evening, and cimetidine 400 mg bid decreased absorption by 14% (p = 0.11). Cimetidine 300 mg qid had no effect on larger doses of alcohol given at dinner. We conclude that many commonly used medications affect gastric ADH, but that the increase in the actual amount of alcohol absorbed is quite small, and demonstrable only under special conditions.
Department of U.S. Medical Affairs and Clinical Development, SmithKline Beecham Pharmaceuticals, Philadelphia, Pennsylvania.
R H
RH
Palmer
W O
WO
Frank
P
P
Nambi
J D
JD
Wetherington
M J
MJ
Fox
D000082:Acetaminophen / Q000494:pharmacology; D000328:Adult; D000426:Alcohol Dehydrogenase / Q000187:drug effects*; D000818:Animals; D002927:Cimetidine / Q000494:pharmacology; D004976:Ethacrynic Acid / Q000494:pharmacology; D000431:Ethanol / Q000097:blood / Q000378:metabolism*; D005260:Female; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D016567:Nizatidine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D012016:Reference Values; D012459:Salicylates / Q000494:pharmacology; D020156:Salicylic Acid
D006635:Histamine H2 Antagonists; D012459:Salicylates; D000082:Acetaminophen; D000431:Ethanol; D002927:Cimetidine; D011899:Ranitidine; D011433:Propranolol; D000426:Alcohol Dehydrogenase; D004976:Ethacrynic Acid; D020156:Salicylic Acid; D016567:Nizatidine