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No clinically significant interactions between the oral direct thrombin inhibitor ximelagatran and amiodarone, atorvastatin, or digoxin
Author(s) -
Dorani H.,
Schützer K.,
Wollbratt M.,
Sarich T. C.,
Eriksson U. G.,
Teng R.,
Ohlsson L.,
Kessler E.,
Wall U.,
Kalies I.,
Hamer J. E.
Publication year - 2004
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2003.11.294
Subject(s) - ximelagatran , atorvastatin , digoxin , pharmacology , direct thrombin inhibitor , medicine , cmax , amiodarone , pharmacokinetics , crossover study , placebo , anesthesia , atrial fibrillation , warfarin , heart failure , dabigatran , alternative medicine , pathology
Background The oral direct thrombin inhibitor ximelagatran has shown clinical benefit in patients with atrial fibrillation at risk of stroke. The potential for interaction of ximelagatran with amiodarone, atorvastatin, or digoxin, was assessed in 3 randomized studies in healthy volunteers. Methods: Study 1 was a placebo‐controlled, parallel‐group study (n=26) with ximelagatran (36mg) or placebo BID for 8 days and amiodarone (single 600mg oral dose) on Day 4. Study 2 was a crossover study (n=16) with atorvastatin (single 40mg oral dose) during one treatment period and ximelagatran (36mg BID for 5 days) plus a single dose of atorvastatin (40mg) on Day 4 during the other treatment period. Study 3 was a double‐blind, crossover study (n=16) with ximelagatran (36mg) or placebo BID for 8 days and digoxin (single 0.5mg dose) on Day 4. Results: For melagatran, the active form of ximelagatran, AUC and C max geometric mean ratios (90% CI) for combined therapy relative to monotherapy with either drug were within or only slightly outside predefined bounds for no interaction. Similarly, no relevant changes were observed for the AUC and C max of amiodarone, atorvastatin, or digoxin. None of the coadministered drugs affected the concentration–effect relationship of melagatran on activated partial thromboplastin time. Conclusions: No clinically significant pharmacokinetic or pharmacodynamic interactions were observed when ximelagatran was administered with amiodarone, atorvastatin, or digoxin. Clinical Pharmacology & Therapeutics (2004) 75 , P78–P78; doi: 10.1016/j.clpt.2003.11.294