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 were orally administered pantoprazole and other proton pump inhibitors, omeprazole and lansoprazole, at 5, 50, or 300 mg/kg/day for 7 days, followed by assays to detect changes in the levels of liver microsomal protein, cytochrome P450, cytochrome b5, NADPH cytochrome c reductase, and drug metabolizing enzyme activities. Increases in total cytochrome P450 contents were evident after a 7-day high-dose administration of all the proton pump inhibitors tested, and the increase by treatment with pantoprazole was less than that with lansoprazole. The three proton 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 proton pump inhibitors. NADPH cytochrome c reductase was induced with omeprazole and pantoprazole. The present results suggest that enzyme induction differs among these proton pump inhibitors not only quantitatively but also qualitatively.
Masubuchi
N
N
Drug Metabolism and Analytical Chemistry Research Laboratory, Daiichi Pharmaceutical Company, Ltd., Tokyo, Japan.
Hakusui
H
H
Okazaki
O
O
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D015153:Blotting, Western; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis; D015786:Cytochromes b5 / Q000096:biosynthesis; D004790:Enzyme Induction; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D064747:Lansoprazole; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D009251:NADPH-Ferrihemoprotein Reductase / Q000096:biosynthesis; D009853:Omeprazole / Q000031:analogs & derivatives / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D000077402:Pantoprazole; D054328:Proton Pump Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D013454:Sulfoxides / Q000494:pharmacology*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000897:Anti-Ulcer Agents; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D013454:Sulfoxides; D064747:Lansoprazole; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D000077402:Pantoprazole; D009251:NADPH-Ferrihemoprotein Reductase; D009853:Omeprazole