| Abstract | 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. |
| Authors | Renli Teng, Troy C Sarich, Ulf G Eriksson, Jennifer E Hamer, Stephen Gillette, Kajs-Marie Schützer, Glenn F Carlson Jr, Peter R Kowey
(Affiliation: Experimental Medicine, AstraZeneca LP, FOC SW1-724, 1800 Concord Pike, P.O. Box 15437, Wilmington, DE 19850-5437, USA.)
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| Journal | Journal of clinical pharmacology
(J Clin Pharmacol)
Vol. 44
Issue 9
Pg. 1063-71
(Sep 2004)
ISSN: 0091-2700 United States |
| PMID | 15317834
(Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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| Chemical References |
- Anti-Arrhythmia Agents
- Anticoagulants
- Azetidines
- Benzylamines
- ximelagatran
- Amiodarone
- desethylamiodarone
- Thrombin
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| Topics |
- Adolescent
- Adult
- Amiodarone
(administration & dosage, analogs & derivatives, blood, pharmacokinetics)
- Anti-Arrhythmia Agents
(administration & dosage, pharmacokinetics)
- Anticoagulants
(administration & dosage, pharmacokinetics)
- Area Under Curve
- Azetidines
(administration & dosage, pharmacokinetics, pharmacology)
- Benzylamines
- Drug Interactions
- Half-Life
- Humans
- Male
- Middle Aged
- Partial Thromboplastin Time
- Regression Analysis
- Single-Blind Method
- Thrombin
(administration & dosage, antagonists & inhibitors, pharmacology)
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