Influence of acid-secretion blockers on gastric and hepatic alcohol dehydrogenase in rat

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Abstract
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.