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Effects of Cimetidine on Blood Ethanol Levels after Alcohol Ingestion and Genetic Polymorphisms of σ‐Alcohol Dehydrogenase in Japanese
Author(s) -
Kawashima Osamu,
Yamauchi Masayoshi,
Maezawa Yoshihiko,
Toda Gotaro
Publication year - 1996
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1996.tb01725.x
Subject(s) - cimetidine , alcohol , ethanol , alcohol dehydrogenase , ethanol metabolism , medicine , pharmacology , chemistry , endocrinology , biochemistry , biology
Administration of cimetidine, an H 2 ‐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 (σ‐ADH) activity. Molecular studies on σ‐ADH showed that a point mutation might occur at position 287 (G → T) of the σ‐ADH gene in Japanese deficient type of σ‐ADH activity. To clarify the relationship between firstpass metabolism of ethanol and polymorphism of σ‐ADH, we analyzed the nucleotide sequence at positions 287 and 294 of σ‐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 Ava II digestion after polymerase chain reaction.