title: The pharmacokinetics and pharmacodynamics of ximelagatran, an oral direct thrombin inhibitor, are unaffected by a single dose of alcohol.
abstract: 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 C(max) (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.
authors.affiliation: Experimental Medicine, AstraZeneca LP, C4C-123, P.O. Box 15437, 1800 Concord Pike, Wilmington, DE 19850, USA.
authors.forename: Troy C
authors.initials: TC
authors.lastname: Sarich
authors.forename: Susanne
authors.initials: S
authors.lastname: Johansson
authors.forename: Kajs-Marie
authors.initials: KM
authors.lastname: Schützer
authors.forename: Ulrika
authors.initials: U
authors.lastname: Wall
authors.forename: Eva
authors.initials: E
authors.lastname: Kessler
authors.forename: Renli
authors.initials: R
authors.lastname: Teng
authors.forename: Ulf G
authors.initials: UG
authors.lastname: Eriksson
mesh_terms: D000328:Adult; D019540:Area Under Curve; D001384:Azetidines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D001596:Benzylamines; D004347:Drug Interactions; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008297:Male; D010314:Partial Thromboplastin Time; D011355:Prodrugs / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D013917:Thrombin / Q000037:antagonists & inhibitors*
chemical_list: D001384:Azetidines; D001596:Benzylamines; D011355:Prodrugs; D000431:Ethanol; C426686:ximelagatran; D013917:Thrombin