Lack of pantoprazole drug interactions in man.
This review summarizes the results of pharmacokinetic and pharmacodynamic drug interaction studies in man with pantoprazole, a new, selective proton pump inhibitor. Different mechanisms have to be considered as causes for potential drug-drug interactions. Proton pump inhibitors (PPIs) in general may alter the absorption of drugs by increasing the intragastric pH. Due to the presence of an imidazole ring, the PPIs of the class of substituted benzimidazole sulfoxides may interfere with the metabolism of other drugs by altering the activity of drug metabolizing enzymes of the cytochrome P450 system, via either induction or inhibition. With the increasing use of PPIs, their interaction potential gains therapeutic importance as was the case with the first and second generation of H2-blockers (cimetidine and ranitidine, respectively). The enhanced selectivity of pantoprazole to the gastric H+/K(+)-ATPase characterizes the new PPI generation. In comparison to omeprazole and lansoprazole, pantoprazole showed a much lower affinity to cytochrome P450 in vitro and a markedly lower potency in the in vivo rat model for interaction with diazepam. In contrast to omeprazole, pantoprazole does not interact with the cytochrome P450 system in man. In the drug interaction studies conducted so far, pantoprazole did not affect the pharmacokinetics or pharmacodynamics of antipyrine, diazepam, digoxin, a hormonal contraceptive, nifedipine, phenytoin, theophylline and warfarin in man. Also pantoprazole neither induced the drug metabolism of antipyrine nor increased urinary excretion of the induction markers D-glucaric acid and 6 beta-hydroxycortisol. Vice versa, the investigated drugs had no relevant influence on the pharmacokinetics of pantoprazole.
Steinijans
V W
VW
Byk Gulden Pharmaceuticals, Konstanz, Germany.
Huber
R
R
Hartmann
M
M
Zech
K
K
Bliesath
H
H
Wurst
W
W
Radtke
H W
HW
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000042:Absorption / Q000187:drug effects; D000983:Antipyrine / Q000493:pharmacokinetics; D001562:Benzimidazoles / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D003278:Contraceptives, Oral, Hormonal / Q000493:pharmacokinetics; D018592:Cross-Over Studies; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003975:Diazepam / Q000493:pharmacokinetics; D004077:Digoxin / Q000493:pharmacokinetics; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008137:Longitudinal Studies; D008297:Male; D009543:Nifedipine / Q000493:pharmacokinetics; D009853:Omeprazole / Q000031:analogs & derivatives; D000077402:Pantoprazole; D010672:Phenytoin / Q000493:pharmacokinetics; D054328:Proton Pump Inhibitors; D013454:Sulfoxides / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D013806:Theophylline / Q000493:pharmacokinetics; D014018:Tissue Distribution / Q000187:drug effects; D014859:Warfarin / Q000493:pharmacokinetics
D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D001562:Benzimidazoles; D003278:Contraceptives, Oral, Hormonal; D054328:Proton Pump Inhibitors; D013454:Sulfoxides; D014859:Warfarin; D010672:Phenytoin; D004077:Digoxin; D003577:Cytochrome P-450 Enzyme System; D013806:Theophylline; D000077402:Pantoprazole; D009543:Nifedipine; D009853:Omeprazole; D003975:Diazepam; D000983:Antipyrine