PANTOPRAZOLE LACKS INTERACTION WITH ANTIPYRINE IN MAN, EITHER BY INHIBITION OR INDUCTION

Substituted benzimidazole inhibitors of the gastric H+/K+-ATPase may i nteract with the cytochrome P450 enzyme system and alter the pharmacok inetics of coadministered drugs, as known for omeprazole. The primary aim of the present studies was to determine whether pantoprazole, a ne w, selective proton pump inhibitor, modifies the plasma concentrations of orally-administered antipyrine, a commonly used marker for mixed h epatic oxidase enzyme activity. In the acute study, 12 healthy male vo lunteers were given a) a single 30 mg i.v. doses of pantoprazole, b) a single 5 mg/kg oral dose of antipyrine, or c) coadministered pantopra zole and antipyrine according to a randomized three-period change-over design. In the chronic study, another 12 volunteers received 40 mg on ce-daily oral doses of pantoprazole on day 3 and on days 5-12, and a s ingle oral 5 mg/kg dose of antipyrine on days 1, 12 and 14. Antipyrine plasma concentrations were measured without pantoprazole (day 1), on the last day of chronic dosing with pantoprazole (day 12) and 48 hours after the last dose of pantoprazole (day 14) to differentiate between inhibition and induction, respectively. Both drugs were well tolerate d and no adverse events or clinically relevant alterations in vital si gns or laboratory parameters were observed during treatment. The point estimates of the respective AUC- and C-max-ratios for antipyrine with and without pantoprazole were 0.99 and 0.98 in the acute study, and 1 .01 and 0.93 on day 12, and 1.04 and 0.99 on day 14 of the chronic stu dy. The corresponding 90%-confidence intervals were all within the equ ivalence range of 0.8-1.25 so that lack of interaction either by inhib ition or induction can be concluded.