The Pharmacokinetics and Pharmacodynamics of Ximelagatran, an Oral Direct Thrombin Inhibitor, Are Unaffected by a Single Dose of Alcohol

Ximelagatran—a direct thrombin inhibitor rapidly converted to its active form, melagatran, after oral administration—is being developed for the prevention and treatment of thromboembolic disease. The pharmacokinetics, pharmacodynamics, and tolerability/safety of ximelagatran following a single 36‐mg oral dose of ximelagatran ± a single oral dose of alcohol (0.5 and 0.6 g ethanol/kg to women and men, respectively) were assessed in a randomized, open‐label, two‐way crossover study (n = 26). The 90% confidence intervals (CIs) and least squares mean estimates for the ratio of ximelagatran plus alcohol to ximelagatran alone for melagatran AUC (1.04 [90% CI = 1.00–1.08]) and Cmax (1.08 [90% CI = 1.03–1.14]) fell within the bounds demonstrating no interaction. Alcohol did not alter the melagatran‐induced prolongation of the activated partial thromboplastin time or the good tolerability/safety profile of ximelagatran. In conclusion, the pharmacokinetics, pharmacodynamics, and tolerability/safety of oral ximelagatran were not affected by alcohol.