EFFECTS OF PANTOPRAZOLE ON XENOBIOTIC-METABOLIZING ENZYMES IN RAT-LIVER MICROSOMES - A COMPARISON WITH OTHER PROTON PUMP INHIBITORS

The effects of pantoprazole on xenobiotic metabolizing enzymes in rat liver microsomes were examined, Groups of female Sprague-Dawley rats w ere orally administered pantoprazole and other proton pump inhibitors, omeprazole and lansoprazole, at 5, 50, or 300 mg/kg/day for 7 days, f ollowed by assays to detect changes in the levels of liver microsomal protein, cytochrome P450, cytochrome b(5), NADPH cytochrome c reductas e, and drug metabolizing enzyme activities. Increases in total cytochr ome P450 contents were evident after a 7-day high-dose administration of all the proton pump inhibitors tested, and the increase by treatmen t with pantoprazole was less than that with lansoprazole. The three pr oton pump inhibitors increased the enzymatic activities and cytochrome P450 enzyme levels of CYP1A, CYP2B, and CYP3A. CYP1A was less induced with pantoprazole than with omeprazole or lansoprazole. In contrast, CYP2B was more strongly induced with pantoprazole than with other prot on pump inhibitors, NADPH cytochrome c reductase was induced with omep razole and pantoprazole, The present results suggest that enzyme induc tion differs among these proton pump inhibitors not only quantitativel y but also qualitatively.