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Rosengren A.M.,Linnaeus University | Rosengren A.M.,SensiKal AB | Karlsson B.C.G.,Linnaeus University | Karlsson B.C.G.,SensiKal AB
Biochemical and Biophysical Research Communications | Year: 2011

Warfarin is an important oral anticoagulant drug that demonstrates a molecular-environment dependent structural diversity. Previous investigations of warfarin's ensemble of isomers in organic solvent-based environments have pointed to the importance of the closed-ring cyclic hemiketal form of the drug in non-polar environments, e.g. the interior of proteins, enzymes and biomembranes. Detection of the presence of these isomers in polar environments has not yet been reported. Here, we demonstrate the presence of the cyclic hemiketal structural form of warfarin under aqueous conditions. This finding underscores the importance considering all structural isomers of this drug when making predictions on warfarin's bioavailability. © 2011 Elsevier Inc. Source


Rosengren A.M.,Linnaeus University | Rosengren A.M.,SensiKal AB | Karlsson B.C.G.,Linnaeus University | Karlsson B.C.G.,SensiKal AB | And 3 more authors.
ACS Medicinal Chemistry Letters | Year: 2012

Warfarin is an anticoagulant drug extensively used in the treatment and prevention of thrombotic disorders. Previous studies have shown that warfarin binds extensively to blood plasma proteins and that only a small fraction of the drug is unbound and thus available for therapeutic function. Both warfarin's narrow therapeutic window and the susceptibility of anticoagulant function to patient-dependent factors necessitate regular monitoring. In this study, we have shown that the lifetimes for each of the various bound and free forms of the drug in blood plasma can be quantified in situ by time-correlated single-photon counting fluorescence spectroscopy over the clinically significant concentration range. A relationship between the blood coagulation and the distribution of fluorescence lifetimes was observed. The in situ detection of clinically relevant concentrations of warfarin in its respective bound and unbound forms could provide a prognostic tool for use in patient treatment. © 2012 American Chemical Society. Source

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