No pharmacokinetic or pharmacodynamic interaction between digoxin and the oral direct thrombin inhibitor ximelagatran in healthy volunteers.
The interaction potential of digoxin and ximelagatran, an oral direct thrombin inhibitor being developed for the prevention and treatment of thromboembolic disease, was investigated in this randomized, double-blind, 2-way crossover study. On 2 separate occasions, healthy female and male volunteers (n = 16) received ximelagatran 36 mg or placebo twice daily for 8 days separated by a 4- to 14-day washout period. All volunteers received a single oral dose of digoxin 0.5 mg on day 4 of both study periods. No interaction between ximelagatran and digoxin was detected in the pharmaco-kinetic parameters (using a 90% confidence interval [CI] of least squares mean estimate ratios), including melagatran (the active form of ximelagatran) AUC(tau) and C(max) and digoxin AUC(t) and C(max). Digoxin did not alter the melagatran-induced prolongation of the activated partial thromboplastin time, and both drugs were well tolerated when administered in combination. In conclusion, no pharmacokinetic or pharmacodynamic interaction between digoxin and ximelagatran was observed in this study.
Sarich
Troy C
TC
Experimental Medicine, AstraZeneca LP, C4C-123, P.O. Box 15437, 1800 Concord Pike, Wilmington, DE 19850, USA.
Schützer
Kajs-Marie
KM
Wollbratt
Maria
M
Wall
Ulrika
U
Kessler
Eva
E
Eriksson
Ulf G
UG
D000284:Administration, Oral; D000328:Adult; D000889:Anti-Arrhythmia Agents / Q000493:pharmacokinetics / Q000494:pharmacology; D000925:Anticoagulants / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D001384:Azetidines / Q000493:pharmacokinetics* / Q000494:pharmacology*; D001596:Benzylamines; D018592:Cross-Over Studies; D004077:Digoxin / Q000493:pharmacokinetics* / Q000494:pharmacology*; D004311:Double-Blind Method; D004347:Drug Interactions; D005260:Female; D005998:Glycine / Q000031:analogs & derivatives* / Q000097:blood / Q000652:urine; D006207:Half-Life; D006801:Humans; D008297:Male; D010314:Partial Thromboplastin Time; D011355:Prodrugs / Q000493:pharmacokinetics / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D000925:Anticoagulants; D001384:Azetidines; D001596:Benzylamines; D011355:Prodrugs; C109573:melagatran; C426686:ximelagatran; D004077:Digoxin; D005998:Glycine