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Br J Clin Pharmacol · Apr 2014
ReviewPharmacogenetic-guided dosing of coumarin anticoagulants: algorithms for warfarin, acenocoumarol and phenprocoumon.
- Talitha I Verhoef, William K Redekop, Ann K Daly, Rianne M F van Schie, Anthonius de Boer, and Anke-Hilse Maitland-van der Zee.
- Department of Pharmaceutical Sciences, Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht University, Utrecht.
- Br J Clin Pharmacol. 2014 Apr 1;77(4):626-41.
AbstractCoumarin derivatives, such as warfarin, acenocoumarol and phenprocoumon are frequently prescribed oral anticoagulants to treat and prevent thromboembolism. Because there is a large inter-individual and intra-individual variability in dose-response and a small therapeutic window, treatment with coumarin derivatives is challenging. Certain polymorphisms in CYP2C9 and VKORC1 are associated with lower dose requirements and a higher risk of bleeding. In this review we describe the use of different coumarin derivatives, pharmacokinetic characteristics of these drugs and differences amongst the coumarins. We also describe the current clinical challenges and the role of pharmacogenetic factors. These genetic factors are used to develop dosing algorithms and can be used to predict the right coumarin dose. The effectiveness of this new dosing strategy is currently being investigated in clinical trials.© 2013 The British Pharmacological Society.
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