title: Lack of pharmacokinetic interaction between pantoprazole and diclofenac.
abstract: The new H+/K+ ATPase inhibitor pantoprazole is extensively metabolized by the liver. As substituted benzimidazoles may potentially interact with the cytochrome P450 system, the influence of pantoprazole on the pharmacokinetics of the NSAID diclofenac was investigated. Diclofenac is widely used in the treatment of rheumatic diseases and is mainly metabolized in the liver by CYP2C9. Twenty-four healthy volunteers (13 male/11 female) completed a randomized crossover study. As test they received orally 40 mg pantoprazole and concomitantly 100 mg diclofenac. As respective references 100 mg diclofenac or 40 mg pantoprazole were given alone. Diclofenac and pantoprazole serum concentrations were measured. Lack of pharmacokinetic interaction was handled as an equivalence problem. The 90% confidence intervals (CI) of the ratios of the primary characteristic AUC and the secondary characteristic Cmax of diclofenac were entirely within the equivalence range of 0.8-1.25. Hence, no influence of pantoprazole on the pharmacokinetics of diclofenac was concluded, either by competition with the CYP2C9 or by the reduction of gastric acid secretion. Vice versa, diclofenac did not affect the pharmacokinetics of pantoprazole. All treatments were safe and well tolerated. No dose adjustment is required during concomitant treatment with diclofenac and pantoprazole.
authors.affiliation: Research Division of Byk Gulden Pharmaceuticals, Konstanz, Germany.
authors.forename: H
authors.initials: H
authors.lastname: Bliesath
authors.forename: R
authors.initials: R
authors.lastname: Huber
authors.forename: V W
authors.initials: VW
authors.lastname: Steinijans
authors.forename: H J
authors.initials: HJ
authors.lastname: Koch
authors.forename: W
authors.initials: W
authors.lastname: Wurst
authors.forename: H
authors.initials: H
authors.lastname: Mascher
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics* / Q000494:pharmacology; D000897:Anti-Ulcer Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D000927:Anticonvulsants / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001562:Benzimidazoles / Q000493:pharmacokinetics / Q000494:pharmacology*; D018592:Cross-Over Studies; D004008:Diclofenac / Q000493:pharmacokinetics* / Q000494:pharmacology; D004311:Double-Blind Method; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D006207:Half-Life; D006801:Humans; D008297:Male; D009853:Omeprazole / Q000031:analogs & derivatives; D000077402:Pantoprazole; D054328:Proton Pump Inhibitors; D013454:Sulfoxides / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D000927:Anticonvulsants; D001562:Benzimidazoles; D004791:Enzyme Inhibitors; D054328:Proton Pump Inhibitors; D013454:Sulfoxides; D004008:Diclofenac; D000077402:Pantoprazole; D009853:Omeprazole