1996 Volume 11 Issue 1 Pages 45-56
The metabolism of omeprazole, a selective inhibitor of H+, K+-ATPase, was studied after oral administration to male rats. In addition to already reported metabolites, 10 unconjugated and 6 conjugated metabolites were isolated from the urine by using TLC and HPLC. The structures of the isolated metabolites were determined by NMR, IR and mass spectrometry. Biotransformation pathways of omeprazole consisted of the oxidation and reduction of the sulfinyl (SO) group, N-oxidation of the pyridine ring, O-demethylation of both methoxy groups, oxidation of the pyridine-5-methyl moiety, aromatic hydroxylation at the 5-position of benzimidazole, and cleavage of the molecule into pyridine and benzimidazole moieties. There was also conjugation with mercapturic acid to carbon at the 2-position of benzimidazole as well as sulfonation and glucuronidation of the hydroxy groups. Based on the structures of the identified metabolites, the metabolic pathways of omeprazole appeared to be very complicated. The tentative metabolic pathways of omeprazole in the rat are presented and discussed.
