期刊
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
卷 77, 期 4, 页码 626-641出版社
WILEY
DOI: 10.1111/bcp.12220
关键词
acenocoumarol; CYP2C9; pharmacogenetics; phenprocoumon; VKORC1; warfarin
资金
- European Community [HEALTH-F2-2009-223062]
- Netherlands Organisation for Health Research and Development (ZonMW)
- Dutch Health Care Insurance Board (CVZ)
- Royal Dutch Pharmacists Association (KNMP)
- EU InnovativeMedicines Initiative (IMI)
- EU
- Dutch Ministry of Health and industry
- GlaxoSmithKline
- Pfizer
Coumarin 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.
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