No influence of food on the pharmacokinetics, pharmacodynamics or tolerability of the 24mg and 36mg oral tablet formulations of ximelagatran

Abstract

Objective: To assess the potential effects of food on the pharmacokinetics and tolerability/safety of ximelagatran, an oral direct thrombin inhibitor developed for the prevention and treatment of thromboembolic disease that is rapidly bioconverted to its active form, melagatran.

Design and study participants: In two open-label, randomised, crossover studies, healthy male and female volunteers received oral ximelagatran as a single 24mg tablet (study 1, n = 30) or a single 36mg tablet (study 2, n = 50). Potential effects of food on the pharmacodynamics (activated partial thromboplastin time; APTT) of the 36mg tablet were also investigated in study 2.

Results: For the 24mg tablet, the 90% confidence intervals (CIs) and least-squares mean estimates for the ratio of the tablet with food to the tablet without food fell within the predefined bounds demonstrating no effect on area under the melagatran concentration-time curve (AUC ratio = 0.94 [90% CI 0.90, 0.99]) or maximum plasma concentration (C(max) ratio = 0.88 [90% CI 0.82, 0.95]). The same result was observed for the 36mg tablet (AUC ratio = 1.07 [90% CI 1.03, 1.12]; C(max) ratio = 1.05 [90% CI 0.98, 1.12]). Melagatran AUC normalised for differences in bodyweight was comparable between women and men administered the 24mg or 36mg tablet without food. In addition, food did not clinically significantly alter the melagatran-induced prolongation of the APTT of the 36mg tablet. Ximelagatran was well tolerated with or without food.

Conclusion: The pharmacokinetics (AUC, C(max)), pharmacodynamics (APTT) and tolerability of melagatran after administration of oral ximelagatran tablets were not affected by food.