No effect of encapsulation on the pharmacokinetics of warfarin.
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.


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(infinity)), AUC to the last evaluable concentration (AUC(t)), and maximum plasma concentration (C(max)) for both R-warfarin (AUC(infinity) [0.93, 1.03], AUC(t) [0.95, 1.03], C(max) [0.90, 1.04]) and S-warfarin (AUC(infinity) [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.
Johansson
Susanne
S
Experimental Medicine, AstraZeneca R&D Mölndal, S-431 83 Mölndal, Sweden. susanne.a.johansson@astrazeneca.com
Ohlsson
Lis
L
Stenhoff
Helene
H
Wåhlander
Karin
K
Cullberg
Marie
M
D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D002214:Capsules; D004311:Double-Blind Method; D006801:Humans; D008297:Male; D008875:Middle Aged; D013237:Stereoisomerism; D013810:Therapeutic Equivalency; D014859:Warfarin / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics*
D002214:Capsules; D014859:Warfarin