Effects of cimetidine on blood ethanol levels after alcohol ingestion and genetic polymorphisms of sigma-alcohol dehydrogenase in Japanese.
Administration of cimetidine, an H2-receptor antagonist increases blood alcohol concentrations. This has been attributed to decreased gastric first-pass metabolism of ethanol caused by cimetidine's inhibitory effect on gastric alcohol dehydrogenase (sigma-ADH) activity. Molecular studies on sigma-ADH showed that a point mutation might occur at position 287 (G --> T) of the sigma-ADH gene in Japanese deficient type of sigma-ADH activity. To clarify the relationship between first-pass metabolism of ethanol and polymorphism of sigma-ADH, we analyzed the nucleotide sequence at positions 287 and 294 of sigma-ADH in 11 individuals who were administered ethanol orally before and after treatment with cimetidine. Higher blood ethanol levels after cimetidine administration were found in 4 of 11 cases (group A), whereas high blood ethanol levels were observed in 7 of 11 cases (B group), irrespective of cimetidine administration. Genetic polymorphisms at position 287 and 294 were not observed in all subjects. Even in 59 Japanese men with various alcoholic liver diseases, no polymorphisms at position 287 were observed by restriction-length polymorphisms with Avail digestion after polymerase chain reaction.
Kawashima
O
O
First Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
Yamauchi
M
M
Maezawa
Y
Y
Toda
G
G
D000328:Adult; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000097:blood* / Q000235:genetics; D001483:Base Sequence / Q000235:genetics; D002927:Cimetidine / Q000494:pharmacology*; D000431:Ethanol / Q000493:pharmacokinetics*; D005753:Gastric Mucosa / Q000201:enzymology; D005838:Genotype; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000235:genetics*; D007564:Japan; D008108:Liver Diseases, Alcoholic / Q000201:enzymology / Q000235:genetics; D008297:Male; D008657:Metabolic Clearance Rate / Q000187:drug effects / Q000235:genetics; D008969:Molecular Sequence Data; D017354:Point Mutation / Q000235:genetics; D012150:Polymorphism, Restriction Fragment Length
D006635:Histamine H2 Antagonists; D007527:Isoenzymes; D000431:Ethanol; D002927:Cimetidine; D000426:Alcohol Dehydrogenase