COMPARATIVE EFFECTS OF OMEPRAZOLE ON XENOBIOTIC-METABOLIZING ENZYMES IN THE RAT AND HUMAN

Omeprazole induces CYP1A in the human liver and gut, which has led to concern about possible side effects, The purpose of this study was to compare the effects of omeprazole on phase 1 and phase 2 enzymes in th e rat and human, Male rats were treated with intraperitoneal (40 or 80 mg/kg) or oral omeprazole (40 mg/kg) for 5 or 14 days, respectively, The activities and amounts of CYP1A, uridine diphosphate-glucuronosylt ransferase, and glutathione transferase were determined in liver and g ut, Enzyme activities were also determined in duodenal biopsy specimen s from six healthy human volunteers before and after treatment with om eprazole (20 mg/day) for 10 days, Treatment with intraperitoneal omepr azole (40 mg/kg; 80 mg/kg) coinduced uridine diphosphate-glucuronosylt ransferase (36%; 66%), glutathione transferase (22%; 50%), and CYP1A ( 26%; 50%) in rat Liver, In rat small intestine, comparable levels of i nduction were observed for uridine diphosphate-glucuronosyltransferase and glutathione transferase; CYP1A was unaffected, Oral omeprazole ha d similar effects, Immunoblotting showed corresponding changes in the amounts of these enzymes, Omeprazole increased the activities of CYP1A (19% to 167%; p = 0.014) and uridine diphosphate-glucuronosyltransfer ase (11% to 68%; p = 0.04) in the duodenal biopsy specimens of all six human volunteers; glutathione transferase was unaffected, Thus, omepr azole coinduced multiple xenobiotic metabolizing enzymes in the rat an d human. The pattern of induction differed in the rat and human, consi stent with known differences in genetic regulatory elements in the two species.