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

Abstract

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 Ki 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.

Key Words:

• alcohol dehydrogenase
• Cimetidine
• ethanol metabolism
• Omeprazole
• Ranitidine