An evaluation of the CYP1A induction potential of pantoprazole in primary rat hepatocytes: a comparison with other proton pump inhibitors.
The ability of pantoprazole to affect the induction of cytochrome P450 (CYP) 1A subfamily was evaluated and compared with two other proton pump inhibitors, omeprazole and lansoprazole, in primary cultured hepatocytes from female Sprague-Dawley rats. The hepatocytes were cultured for 2 days, followed by treatment for 2 days with the proton pump inhibitors at 2, 5 and 10 microM, concentrations that are similar to plasma concentrations found in rats in vivo. The CYP1A inducer 3-methylcholanthrene (at 1 microM) was also evaluated as a positive control. Induction potentials of these chemicals for CYP1A were determined by 7-ethoxyresorufin O-deethylase activity and isozyme contents. The results showed that for CYP1A induction, the rank ordering in induction potential was consistently lansoprazole > omeprazole > pantoprazole. The results are consistent with the existing rat in vivo data, i.e. pantoprazole has lower CYP1A induction potential than omeprazole and lansoprazole.
Masubuchi
N
N
Drug Metabolism and Analytical Chemistry Research Laboratory, Daiichi Pharmaceutical Co., Ltd., Tokyo, Japan.
Okazaki
O
O
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000187:drug effects* / Q000378:metabolism; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D064747:Lansoprazole; D008099:Liver / Q000187:drug effects* / Q000201:enzymology*; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology; D009853:Omeprazole / Q000031:analogs & derivatives / Q000494:pharmacology; D000077402:Pantoprazole; D054328:Proton Pump Inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D013454:Sulfoxides / Q000494:pharmacology*
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D013454:Sulfoxides; D064747:Lansoprazole; D000077402:Pantoprazole; D019363:Cytochrome P-450 CYP1A1; D009853:Omeprazole