Comparison of the bioavailabilities and anticoagulant activities of two warfarin formulations

Abstract

Changes in the British Pharmacopoeia dissolution time requirements have necessitated reformulation of warfarin sodium (Marevan). The old and new formulations were compared with each other in 8 healthy volunteers given a single 15-mg dose of each in a cross-over study and also in 19 patients receiving warfarin therapy. In the volunteer study, a significant but small increase in bioavailability was observed for the new formulation. The effects of the 2 formulations on the prothrombin ratio and on clotting factors II, VII, IX and X were not significantly different. Irrespective of formulation, the greatest changes in factors II, VII and X were observed after the 1st dose of warfarin. With factor IX, the greatest response was observed after the 2nd dose. The clinical study in patients confirmed that the old and new formulations of Marevan are interchangeable on a dose for dose basis. A sensitive semiautomated warfarin assay technique is described.