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 p ump inhibitors, omeprazole and lansoprazole, in primary cultured hepat ocytes from female Sprague-Dawley rats. The hepatocytes were cultured for 2 days, followed by treatment for 2 days with the proton pump inhi bitors at 2, 5 and 10 mu M, concentrations that are similar to plasma concentrations found in rats in vivo. The CYP1A inducer 3-methylcholan threne (at 1 mu M) was also evaluated as a positive control. Induction potentials of these chemicals for CYP1A were determined by 7-ethoxyre sorufin O-deethylase activity and isozyme contents. The results showed that for CYP1A induction, the rank ordering in induction potential wa s consistently lansoprazole > omeprazole > pantoprazole. The results a re consistent with the existing rat in vivo data, i.e. pantoprazole ha s lower CYP1A induction potential than omeprazole and lansoprazole. (C ) 1997 Elsevier Science Ireland Ltd.