title: Pantoprazole lacks interaction with antipyrine in man, either by inhibition or induction.
abstract: Substituted benzimidazole inhibitors of the gastric H+/K(+)-ATPase may interact with the cytochrome P450 enzyme system and alter the pharmacokinetics of coadministered drugs, as known for omeprazole. The primary aim of the present studies was to determine whether pantoprazole, a new, selective proton pump inhibitor, modifies the plasma concentrations of orally-administered antipyrine, a commonly used marker for mixed hepatic oxidase enzyme activity. In the acute study, 12 healthy male volunteers 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 pantoprazole and antipyrine according to a randomized three-period change-over design. In the chronic study, another 12 volunteers received 40 mg once-daily oral doses of pantoprazole on day 3 and on days 5-12, and a single 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 tolerated and no adverse events or clinically relevant alterations in vital signs or laboratory parameters were observed during treatment. The point estimates of the respective AUC- and Cmax-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 study.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Center for Cardiovascular Pharmacology, Mainz, Germany.
authors.forename: C
authors.initials: C
authors.lastname: De Mey
authors.forename: I
authors.initials: I
authors.lastname: Meineke
authors.forename: V W
authors.initials: VW
authors.lastname: Steinijans
authors.forename: R
authors.initials: R
authors.lastname: Huber
authors.forename: M
authors.initials: M
authors.lastname: Hartmann
authors.forename: H
authors.initials: H
authors.lastname: Bliesath
authors.forename: W
authors.initials: W
authors.lastname: Wurst
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000284:Administration, Oral; D000328:Adult; D000983:Antipyrine / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001562:Benzimidazoles / Q000097:blood / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D004347:Drug Interactions; D006207:Half-Life; D006801:Humans; D007262:Infusions, Intravenous; D008137:Longitudinal Studies; D008297:Male; D008657:Metabolic Clearance Rate; D009853:Omeprazole / Q000031:analogs & derivatives; D000077402:Pantoprazole; D054328:Proton Pump Inhibitors; D012107:Research Design; D013454:Sulfoxides / Q000097:blood / Q000494:pharmacology*
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D054328:Proton Pump Inhibitors; D013454:Sulfoxides; D000077402:Pantoprazole; D009853:Omeprazole; D000983:Antipyrine