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The optimization of coumarin anticoagulant therapy: pharmacogenetics and computer assisted dose finding

26 June 2009

PhD ceremony: M.J. Beinema, 13.15 uur, Academiegebouw, Broerstraat 5, Groningen

Thesis: The optimization of coumarin anticoagulant therapy: pharmacogenetics and computer assisted dose finding

Promotor(s): prof. J.R.B.J. Brouwers, prof. J. van der Meer †

Faculty: Mathematics and Natural Sciences


Pharmacogenetics is the field of research that describes the influence of variations of DNA characteristics on drug response. Maarten Beinema studied the influence of VKORC1 and CYP2C9 polymorphisms on the different coumarins warfarin, acenocoumarol and phenprocoumon. The combination of VKORC1 and CYP2C9 polymorphisms explains a major part of the inter-individual differences of coumarin dosages. The effects of CYP2C9 polymorphisms on the pharmacokinetics and anticoagulant response are least pronounced in the case of phenprocoumon.

He found that within a group of patients with the CYP2C9 mutation, only those patients who concomitantly used a NSAID had an INR value exceeding 4.9. These patients have a higher risk of bleeding complications.

He describes the development and validation of a new coumarin dose finding algorithm. In order to validate the algorithm, he compared the outcomes of the algorithm with the three existing algorithms in the Netherlands. The algorithm performance was comparable with the other existing programs and in some aspects it performed even better. The algorithm generated significantly more accepted automated proposals. Therefore, the algorithm may improve the quality of coumarin therapy of anticoagulation clinics and may be more cost-effective. Hee also describes the development and the performances of an Internet application The new oral anticoagulants dabigatran and rivaroxaban are possibly the anticoagulant drugs of the future. Pharmaco-economical studies may decide which drug should be preferred in future. Beinema provides a review on the current situation.


Last modified:15 September 2017 3.39 p.m.

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