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No effect of encapsulation on the pharmacokinetics of warfarin
Author(s) -
Johansson Susanne,
Ohlsson Lis,
Stenhoff Helene,
Wåhlander Karin,
Cullberg Marie
Publication year - 2005
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.441
Subject(s) - ximelagatran , warfarin , bioequivalence , pharmacokinetics , crossover study , pharmacology , area under the curve , medicine , direct thrombin inhibitor , dabigatran , atrial fibrillation , alternative medicine , pathology , placebo
Background . In double‐blind comparator studies with the oral direct thrombin inhibitor (oral DTI) ximelagatran, warfarin (Coumadin®) was administered in encapsulated form in order to maintain patient and investigator blinding. This open, randomized, two‐way crossover study was conducted to determine whether the encapsulated warfarin tablets (Coumadin®) used in the ximelagatran studies are bioequivalent to nonencapsulated, commercially available warfarin (Coumadin®) tablets. Methods and Results . Eighteen healthy men received two 2.5 mg tablets of encapsulated warfarin and two 2.5 mg tablets of nonencapsulated warfarin as single oral doses, 14 days apart. The 90% confidence intervals for the mean treatment ratio (encapsulated tablet/nonencapsulated tablet) fell within the limits considered to reflect bioequivalence (0.80, 1.25) for total area under the plasma concentration‐versus‐time curve ( AUC ∞ ), AUC to the last evaluable concentration ( AUC t ), and maximum plasma concentration ( C max ) for both R‐warfarin ( AUC ∞ [0.93, 1.03], AUC t [0.95, 1.03], C max [0.90, 1.04]) and S‐warfarin ( AUC ∞ [0.93, 1.03], AUC t [0.94, 1.03], C max [0.90, 1.06]). Conclusions . The encapsulated form of warfarin (Coumadin®) used in comparator studies with the oral DTI ximelagatran is bioequivalent to the nonencapsulated, commercially available form of warfarin (Coumadin®). Thus, the results of ximelagatran clinical trials with encapsulated warfarin can be generalized to the commercially available form. Copyright © 2005 John Wiley & Sons, Ltd.