INFLUENCE OF H-2-RECEPTOR-INHIBITOR AND PROTON PUMP INHIBITOR ON SOMEFUNCTIONS OF THE OXIDATIVE AND CONJUGATIVE DRUG-METABOLISM

There are numerous investigations describing the influence of histamin e H-2-receptor antagonists and proton pump inhibitors on cytochrome P4 50-mediated hepatic oxydative and conjugative drug metabolizing enzyme s. The aim of this study was to investigate the influence of the H-2-r eceptor blockers cimetidine, ranitidine, famotidine, nizatidine and of the proton pump inhibitors omeprazole and lansoprazole on the acetyla tion capacity and on different microsomal monooxygenases of the rat li ver. The experiments were performed in two randomized studies with mal e Wistar rats after a 7-day pretreatment of the animals with antisecre tory, equipotent doses of the investigational products. The activities of the arylamine N-acetyltransferase (NAT) and the microsomal enzymes were determined in vitro. Cimetidine and ranitidine decreased the act ivity of NAT significantly, no effect on this enzyme was observed afte r nizatidine. Small doses of famotidine tended to lower, high doses of famotidine tended to enhance the NAT activity. The proton pump inhibi tor omeprazole significantly increased the NAT activity, lansoprazole evoked a small increase of the enzyme activity. Ethyl-resorufin O-deet hylase (EROD) and pentylresorufin O-depentylase (PROD) were sensitive to cimetidine, ranitidine and famotidine. Only omeprazole and lansopra zole treatment inhibited the dextromethorphan O-demethylase (DXDM) act ivity.