The pharmacokinetics and metabolism of the direct thrombin inhibitor dabigatran (BIBR 953 ZW, beta-alanine, N-[[2-[[[4-(aminoiminomethyl)phenyl]amino]methyl]-1-methyl-1H-benzimidazol-5-yl]carbonyl]-N-2-pyridinyl) were studied in 10 healthy males, who received 200 mg of [(14)C]dabigatran etexilate (BIBR 1048 MS, the oral prodrug of dabigatran) or an i.v. infusion of 5 mg of [(14)C]dabigatran. Radioactivity was measured in plasma, urine, and feces over 1 week. The metabolite pattern was analyzed by high-performance liquid chromatography with on-line radioactivity detection, and metabolite structures were elucidated by mass spectrometry. Dabigatran etexilate was rapidly converted to dabigatran, with peak plasma dabigatran concentrations being attained after approximately 1.5 h; the bioavailability of dabigatran after p.o. administration of dabigatran etexilate was 7.2%. Dabigatran was predominantly excreted in the feces after p.o. treatment and in the urine after i.v. treatment. The mean terminal half-life of dabigatran was approximately 8 h. The predominant metabolic reaction was esterase-mediated hydrolysis of dabigatran etexilate to dabigatran. Phase I metabolites accounted for