title: Lack of pharmacodynamic and pharmacokinetic interaction between pantoprazole and phenprocoumon in man.
abstract: OBJECTIVE
  Pantoprazole is a selective proton pump inhibitor characterized by a low potential to interact with the cytochrome P450 enzymes in man. Due to the clinical importance of an interaction with anticoagulants, this study was carried out to investigate the possible influence of pantoprazole on the pharmacodynamics and pharmacokinetics of phenprocoumon.
  
  
  METHODS
  Sixteen healthy male subjects were given individually adjusted doses of phenprocoumon to reduce prothrombin time ratio (Quick method) to about 30-40% of normal within the first 5-9 days and to maintain this level. The individual maintenance doses remained unaltered from day 9 on and were administered until day 15. Additionally, on study days 11-15, pantoprazole 40 mg was given per once daily. As a pharmacodynamic parameter, the prothrombin time ratio was determined on days 9 and 10 (reference value) and on days 14 and 15 (test value), and the ratio test/reference was evaluated according to equivalence criteria.
  
  
  RESULTS
  The equivalence ratio (test/reference) for prothrombin time ratio was 1.02 (90% confidence interval 0.95-1.09), thus fulfilling predetermined bioequivalence criteria (0.70-1.43). The pharmacokinetic characteristics AUC0-24h and Cmax of S(-)- and R(+)-phenprocoumon were also investigated using equivalence criteria. Equivalence ratios and confidence limits of AUC0-24h and of Cmax of S(-)-phenprocoumon (0.93, 0.87-1.00 for AUC0-24h; 0.95, 0.88-1.03 for Cmax) and of R(+)-phenprocoumon (0.89, 0.82-0.96; 0.9, 0.83-0.98) were within the accepted range of 0.8-1.25.
  
  
  CONCLUSIONS
  Pantoprazole does not interact with the anticoagulant phenprocoumon on a pharmacodynamic or pharmacokinetic level. Concomitant treatment was well tolerated.
authors.affiliation: Institut für klinische Pharmakologie Bobenheim, Prof. Dr. Lücker GmbH, Grünstadt, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Ehrlich
authors.forename: H
authors.initials: H
authors.lastname: Fuder
authors.forename: M
authors.initials: M
authors.lastname: Hartmann
authors.forename: G
authors.initials: G
authors.lastname: Wieckhorst
authors.forename: W
authors.initials: W
authors.lastname: Timmer
authors.forename: R
authors.initials: R
authors.lastname: Huber
authors.forename: M
authors.initials: M
authors.lastname: Birkel
authors.forename: H
authors.initials: H
authors.lastname: Bliesath
authors.forename: V W
authors.initials: VW
authors.lastname: Steinijans
authors.forename: W
authors.initials: W
authors.lastname: Wurst
authors.forename: P W
authors.initials: PW
authors.lastname: Lücker
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000328:Adult; D000925:Anticoagulants / Q000493:pharmacokinetics*; D001562:Benzimidazoles / Q000494:pharmacology*; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D004347:Drug Interactions; D006801:Humans; D008297:Male; D009853:Omeprazole / Q000031:analogs & derivatives; D000077402:Pantoprazole; D010644:Phenprocoumon / Q000493:pharmacokinetics* / Q000494:pharmacology; D054328:Proton Pump Inhibitors; D013237:Stereoisomerism; D013454:Sulfoxides / Q000494:pharmacology*
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000925:Anticoagulants; D001562:Benzimidazoles; D054328:Proton Pump Inhibitors; D013454:Sulfoxides; D003577:Cytochrome P-450 Enzyme System; D000077402:Pantoprazole; D009853:Omeprazole; D010644:Phenprocoumon