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ACS Med Chem Lett. 2012 Jun 20;3(8):650-2. doi: 10.1021/ml300112e. eCollection 2012 Aug 09.

Monitoring the distribution of warfarin in blood plasma.

ACS medicinal chemistry letters

Annika M Rosengren, Björn C G Karlsson, Ian A Nicholls

Affiliations

  1. Bioorganic and Biophysical Chemistry Laboratory, School of Natural Sciences, Linnæus University , SE-391 82 Kalmar, Sweden ; SensiKal AB , Öltappargränd 10, SE-393 64 Kalmar, Sweden.
  2. Bioorganic and Biophysical Chemistry Laboratory, School of Natural Sciences, Linnæus University , SE-391 82 Kalmar, Sweden ; SensiKal AB , Öltappargränd 10, SE-393 64 Kalmar, Sweden ; Department of Chemistry, Uppsala University , SE-751 23 Uppsala, Sweden.

PMID: 24900525 PMCID: PMC4025853 DOI: 10.1021/ml300112e

Abstract

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.

Keywords: TCSPC; coagulation; fluorescence spectroscopy; plasma; warfarin

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