LACK OF PHARMACODYNAMIC AND PHARMACOKINETIC INTERACTION BETWEEN PANTOPRAZOLE AND PHENPROCOUMON IN MAN

Objective: Pantoprazole is a selective proton pump inhibitor character ized by a low potential to interact with the cytochrome P450 enzymes i n man. Due to the clinical importance of an interaction with anticoagu lants, this study was carried out to investigate the possible influenc e of pantoprazole on the pharmacodynamics and pharmacokinetics of phen procoumon. Methods: Sixteen healthy male subjects were given individua lly 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 unal tered 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 c riteria. Results: The equivalence ratio (test/reference) for prothromb in time ratio was 1.02 (90% confidence interval 0.95-1.09), thus fulfi lling predetermined bioequivalence criteria (0.70-1.43). The pharmacok inetic characteristics AUC(0-24h) and C-max of S(-)- and R(+)-phenproc oumon were also investigated using equivalence criteria. Equivalence r atios and confidence limits of AUC(0-24h) and of C-max of S(-)-phenpro coumon (0.93, 0.87-1.00 for AUC(0-24h); 0.95, 0.88-1.03 for C-max) and of R(+)-phenprocoumon (0.89, 0.82-0.96; 0.9, 0.83-0.98) were within t he accepted range of 0.8-1.25. Conclusion: Pantoprazole does not inter act with the anticoagulant phenprocoumon on a pharmacodynamic or pharm acokinetic level. Concomitant treatment was well tolerated.