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Pharmacogenetic characteristics of patients with complicated phenprocoumon dosing

  • Pharmacogenetics
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

Abstract

Purpose

Anticoagulation therapy with coumarins necessitates a strict individualization of dosing. Whereas the impacts of the cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase (VKORC1) polymorphisms on warfarin dosing are clearly established, the role of these genetic variants on dosing and the safe use of phenprocoumon are less well investigated and, to a certain degree, controversial.

Methods

We studied the most frequent functional polymorphisms of VKORC1, CYP2C9, and CYP3A5 in 60 consecutive patients demonstrating complicated phenprocoumon-mediated anticoagulation and in 120 controls.

Results

The frequencies of the less active VKORC1 haplotype A-group alleles (p < 0.0001) and of CYP2C9 genotypes with two variant alleles (p = 0.035) were higher in the patient cohort than in the control group, while the frequency of patients carrying only one variant CYP2C9 allele was unchanged relative to the control subjects (RR 1.2; p = 0.49).

Conclusion

The data suggest a fundamental role of VKORC1 haplotypes and a minor role of CYP2C9 variants in the anticoagulation property of phenprocoumon.

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Authors and Affiliations

  1. Department of Cardiology/Angiology, Protestant Community Hospital, Ludwigslust, Germany

    D. Werner & A. Wuerfel

  2. Institute of Clinical and Experimental Pharmacology and Toxicology, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246, Hamburg, Germany

    U. Werner, T. Eschenhagen & T. Rau

  3. Institute of Laboratory Medicine, Helios-Hospital, Schwerin, Germany

    A. Grosch & H. G. Lestin

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  1. D. Werner
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  2. U. Werner
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  3. A. Wuerfel
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  4. A. Grosch
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  5. H. G. Lestin
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  6. T. Eschenhagen
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  7. T. Rau
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Correspondence to T. Rau.

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Werner, D., Werner, U., Wuerfel, A. et al. Pharmacogenetic characteristics of patients with complicated phenprocoumon dosing. Eur J Clin Pharmacol 65, 783–788 (2009). https://doi.org/10.1007/s00228-009-0639-2

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  • DOI: https://doi.org/10.1007/s00228-009-0639-2

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