caa a22 4500 477056113 CHVBK 20180405111346.0 cr unu---uuuuu 170330e19961201xx s 000 0 eng 10.1007/s002280050198 doi (NATIONALLICENCE)springer-10.1007/s002280050198 Lack of pharmacodynamic and pharmacokinetic interaction between pantoprazole and phenprocoumon in man [Elektronische Daten] [A. Ehrlich, H. Fuder, M. Hartmann, G. Wieckhorst, W. Timmer, R. Huber, M. Birkel, H. Bliesath, V. W. Steinijans, W. Wurst, P. W. Lücker] 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. Conclusion: Pantoprazole does not interact with the anticoagulant phenprocoumon on a pharmacodynamic or pharmacokinetic level. Concomitant treatment was well tolerated. Springer-Verlag Berlin Heidelberg, 1996 Key words Pantoprazole nationallicence Proton pump inhibitor drug interaction nationallicence oral anticoagulant phenprocoumon nationallicence pharmacodynamics nationallicence pharmacokinetics nationallicence Ehrlich A. Institut für klinische Pharmakologie Bobenheim, Prof. Dr. Lücker GmbH, Richard Wagner-Str. 20, D-67269 Grünstadt, Germany Tel.: (6359)8990; Fax: (6359)899-226, DE aut Fuder H. Institut für klinische Pharmakologie Bobenheim, Prof. Dr. Lücker GmbH, Richard Wagner-Str. 20, D-67269 Grünstadt, Germany Tel.: (6359)8990; Fax: (6359)899-226, DE aut Hartmann M. Byk Gulden Pharmaceuticals, POB 100310, D-78403 Konstanz, Germany, DE aut Wieckhorst G. Institut für klinische Pharmakologie Bobenheim, Prof. Dr. Lücker GmbH, Richard Wagner-Str. 20, D-67269 Grünstadt, Germany Tel.: (6359)8990; Fax: (6359)899-226, DE aut Timmer W. Institut für klinische Pharmakologie Bobenheim, Prof. Dr. Lücker GmbH, Richard Wagner-Str. 20, D-67269 Grünstadt, Germany Tel.: (6359)8990; Fax: (6359)899-226, DE aut Huber R. Byk Gulden Pharmaceuticals, POB 100310, D-78403 Konstanz, Germany, DE aut Birkel M. Institut für klinische Pharmakologie Bobenheim, Prof. Dr. Lücker GmbH, Richard Wagner-Str. 20, D-67269 Grünstadt, Germany Tel.: (6359)8990; Fax: (6359)899-226, DE aut Bliesath H. Byk Gulden Pharmaceuticals, POB 100310, D-78403 Konstanz, Germany, DE aut Steinijans V. W. Byk Gulden Pharmaceuticals, POB 100310, D-78403 Konstanz, Germany, DE aut Wurst W. Byk Gulden Pharmaceuticals, POB 100310, D-78403 Konstanz, Germany, DE aut Lücker P. W. Institut für klinische Pharmakologie Bobenheim, Prof. Dr. Lücker GmbH, Richard Wagner-Str. 20, D-67269 Grünstadt, Germany Tel.: (6359)8990; Fax: (6359)899-226, DE aut https://doi.org/10.1007/s002280050198 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s002280050198 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Ehrlich A. Institut für klinische Pharmakologie Bobenheim, Prof. Dr. Lücker GmbH, Richard Wagner-Str. 20, D-67269 Grünstadt, Germany Tel.: (6359)8990; Fax: (6359)899-226, DE aut NATIONALLICENCE 700 1- Fuder H. Institut für klinische Pharmakologie Bobenheim, Prof. Dr. Lücker GmbH, Richard Wagner-Str. 20, D-67269 Grünstadt, Germany Tel.: (6359)8990; Fax: (6359)899-226, DE aut NATIONALLICENCE 700 1- Hartmann M. Byk Gulden Pharmaceuticals, POB 100310, D-78403 Konstanz, Germany, DE aut NATIONALLICENCE 700 1- Wieckhorst G. Institut für klinische Pharmakologie Bobenheim, Prof. Dr. Lücker GmbH, Richard Wagner-Str. 20, D-67269 Grünstadt, Germany Tel.: (6359)8990; Fax: (6359)899-226, DE aut NATIONALLICENCE 700 1- Timmer W. Institut für klinische Pharmakologie Bobenheim, Prof. Dr. Lücker GmbH, Richard Wagner-Str. 20, D-67269 Grünstadt, Germany Tel.: (6359)8990; Fax: (6359)899-226, DE aut NATIONALLICENCE 700 1- Huber R. Byk Gulden Pharmaceuticals, POB 100310, D-78403 Konstanz, Germany, DE aut NATIONALLICENCE 700 1- Birkel M. Institut für klinische Pharmakologie Bobenheim, Prof. Dr. Lücker GmbH, Richard Wagner-Str. 20, D-67269 Grünstadt, Germany Tel.: (6359)8990; Fax: (6359)899-226, DE aut NATIONALLICENCE 700 1- Bliesath H. Byk Gulden Pharmaceuticals, POB 100310, D-78403 Konstanz, Germany, DE aut NATIONALLICENCE 700 1- Steinijans V. W. Byk Gulden Pharmaceuticals, POB 100310, D-78403 Konstanz, Germany, DE aut NATIONALLICENCE 700 1- Wurst W. Byk Gulden Pharmaceuticals, POB 100310, D-78403 Konstanz, Germany, DE aut NATIONALLICENCE 700 1- Lücker P. W. Institut für klinische Pharmakologie Bobenheim, Prof. Dr. Lücker GmbH, Richard Wagner-Str. 20, D-67269 Grünstadt, Germany Tel.: (6359)8990; Fax: (6359)899-226, DE aut Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer