Premium
A Pharmacokinetic Study of the Combined Administration of Amiodarone and Ximelagatran, an Oral Direct Thrombin Inhibitor
Author(s) -
Teng Renli,
Sarich Troy C.,
Eriksson Ulf G.,
Hamer Jennifer E.,
Gillette Stephen,
Schützer KajsMarie,
Carlson Glenn F.,
Kowey Peter R.
Publication year - 2004
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270004268446
Subject(s) - ximelagatran , amiodarone , cmax , direct thrombin inhibitor , pharmacokinetics , medicine , pharmacology , oral administration , anesthesia , placebo , confidence interval , anticoagulant , warfarin , atrial fibrillation , alternative medicine , dabigatran , pathology
The oral direct thrombin inhibitor ximelagatran is being developed for the prevention and treatment of thromboembolism. This single‐blind, randomized, placebo‐controlled, parallel‐group study investigated the potential for the interaction of ximelagatran (36 mg every 12 hours for 8 days, measured as its active form melagatran in blood) and amiodarone (single 600‐mg oral dose on day 4) in healthy male subjects ( n = 26). For amiodarone + ximelagatran versus amiodarone + placebo, geometric mean ratios (90% confidence intervals for amiodarone AUC 0–120 and C max were 0.87 (0.69–1.08) and 0.86 (0.66–1.11), respectively. For desethylamiodarone, the principal metabolite of amiodarone, the corresponding ratios were 1.00 (0.89–1.12) for AUC 0–120 and 0.92 (0.77–1.09) for C max. The geometric mean ratios (90% confidence intervals) for ximelagatran + amiodarone versus ximelagatran were 1.21 (1.17–1.25) for melagatran AUC 0–12 and 1.23 (1.18–1.28) for melagatran C max. These confidence intervals were within or only slightly outside the interval, suggesting no interaction (0.8–1.25 for the effect of amiodarone on melagatran and 0.7–1.43 for the effect of melagatran on amiodarone or desethylamiodarone). Amiodarone did not affect the concentration‐effect relationship of melagatran on activated partial thromboplastin time. Ximelagatran was well tolerated when coadministered with a single dose of amiodarone. Evaluation of the safety of the combination is needed to confirm that the relatively small pharmacokinetic changes in this study are of no clinical significance.