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 K(m) 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 K(m) gastric ADH with a K(i) of 0. 167 mmol l-1 and a competitive inhibition of high K(m) gastric ADH with a K(i) 2.3 mmol l-1. Ranitidine was found to present non-competitive inhibition only on low K(m) gastric ADH with a K(i) of 12 mmol l-1. Omeprazole affects only low K(m) gastric ADH with a K(i) 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 K(i) 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 ADH(s) activity and probably on first-pass metabolism.