Influence of acid-secretion blockers on gastric and hepatic alcohol dehydrogenase in rat.
The effects of Cimetidine, Ranitidine, and Omeprazole on gastric and hepatic alcohol-dehydrogenase (ADH) activity was studied in rat. Two apparent values for Km were found for gastric ADH (220 mmol l-1 and 1043 mmol l-1 respectively) and one for hepatic ADH (0.54 mmol l-1). Cimetidine was shown to exert an uncompetitive inhibition of low Km gastric ADH with a Ki of 0.167 mmol l-1 and a competitive inhibition of high Km gastric ADH with a Ki 2.3 mmol l-1. Ranitidine was found to present non-competitive inhibition only on low Km gastric ADH with a Ki of 12 mmol l-1. Omeprazole affects only low Km gastric ADH with a Ki of 5.6 mmol l-1 and presents a linear-mixed type of inhibition. Hepatic ADH was shown to be competitively inhibited only by Cimetidine with a Ki of 6.0 mmol l-1 whereas no inhibition for either Ranitidine and Omeprazole was observed. These results confirm the inhibitory action of Cimetidine on both gastric and hepatic ADH; Ranitidine and Omeprazole show minor effects on ADHS activity and probably on first-pass metabolism.
Pozzato
G
G
Instituto di Patologia Medica, University School of Medicine, Trieste, Italy.
Stebel
M
M
Lunazzi
G
G
Moretti
M
M
Franzin
F
F
D000426:Alcohol Dehydrogenase / Q000378:metabolism*; D000818:Animals; D002927:Cimetidine / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology*; D007527:Isoenzymes / Q000378:metabolism; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D009853:Omeprazole / Q000494:pharmacology*; D011899:Ranitidine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D007527:Isoenzymes; D002927:Cimetidine; D011899:Ranitidine; D000426:Alcohol Dehydrogenase; D009853:Omeprazole