Pharmacokinetic and pharmacodynamic effects of comedication of clopidogrel and dabigatran etexilate in healthy male volunteers

• DOI: 10.1007/s00228-012-1304-8
• Publication Date: 2012-07-10T13:51:44Z
• Authors: Sebastian Härtter; Regina Sennewald; Cornelia Schepers; Sybille Baumann; Holger Fritsch; Jeffrey Friedman
• Keywords: Pharmacodynamics; Crossover study; Concomitant

To evaluate the pharmacokinetic and pharmacodynamic effects of concomitant administration single loading doses clopidogrel or multiple with dabigatran etexilate.This was an open-label trial in healthy male subjects. In part 1 (pilot, n = 8) 3 (n 12), a dose (300 600 mg, respectively) given concomitantly etexilate at steady state; 2 randomized, multiple-dose, crossover study test treatment being state [300 mg on day 1, then 75 once daily (qd)] dabigatran.Bioavailability moderately increased when 3) administered 150 twice (bid). Test/reference ratios for AUC(τ,ss) were 135% (90% CI 107-169%) 132% 112-156%), respectively. Steady-state dosing qd bid (part 2) demonstrated minor pharmacokinetics (AUC(τ,ss) ratio test/reference: 91.9%, 90% 78.7-107%) its pharmacokinetic/pharmacodynamic relationships (activated partial thromboplastin time, ecarin clotting thrombin time). Similarly, bioavailability remained unchanged by chronic 3: test/reference AUC(0-24) 103%; 80.3-131%), as did inhibition platelet aggregation.When concomitantly, clinically relevant not appear to have significant profiles either agent.