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Obesity is associated with a slower response to initial phenprocoumon therapy whereas CYP2C9 genotypes are not

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

Abstract

Background

Initiation of phenprocoumon therapy is associated with a variable individual response. The CYP2C9 genotype has been shown to influence the response to warfarin therapy, but such an effect on phenprocoumon therapy remains uncertain.

Method

Two hundred sixty hospital patients started on phenprocoumon were recruited for this study. Body mass index (BMI), waist and hip circumference, dietary habits, comorbidity, and comedication were initially assessed. A 5′ exonuclease assay (TaqManR) was used to analyze the presence of five polymorphisms of the CYP2C9 gene in each of the study patients. Study endpoints included the time necessary to achieve the international normalized ratio (INR) target (INR >2) and the total drug amount required to attain target INR. For 250 of 260 patients, the subsequent required daily maintenance dose of phenprocoumon was also recorded.

Results

Both the necessary time and total dose required to attain target INR correlated significantly with BMI. The leaner the patient, the shorter the required time interval [BMI <22 (n=31), 5.48±2.49 days; BMI 22–25 (n=70), 6.09±2.40; BMI 25–30 (n=113), 6.76±3.61; BMI >30 (n=46), 8.50±5.75; p=0.001] and the lower the required dosage until the therapeutic range was achieved [BMI <22 (n=31), 23.8±12.1 mg; BMI 22–25 (n=70), 25.9±11.4 mg; BMI 25–30 (n=113), 29.6±25.2; BMI >30 (n=46), 35.8±19.7; p=0.027]. Overweight and waist circumference as a surrogate marker for abdominal fat were also associated significantly with these two parameters. Moreover, obesity was associated with a lower body-weight-adjusted maintenance dosage. All CYP2C9 genotypes that were tested failed to reveal an association with individual response variability.

Conclusion

Patient obesity appears to directly correspond to the amount of phenprocoumon required during initiation of therapy. The CYP2C9 genotype was not shown to influence the necessary therapeutic dosage.

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Acknowledgements

This study was supported by the START program of the University Hospital of Aachen and is part of the doctoral thesis of C. Meyer zu Schwabedissen.

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Authors and Affiliations

  1. Interdisciplinary Intermediate Care, University Hospital of Aachen, RWTH Aachen, 52057, Aachen, Germany

    Jan R. Ortlepp

  2. Medical Clinic I, University Hospital of Aachen, RWTH Aachen, 52057, Aachen, Germany

    Cordula Meyer zu Schwabedissen, Vera Mevissen, Fabian Schmitz, Rainer Hoffmann & Jan R. Ortlepp

  3. Institute of Human Genetics, University Hospital of Aachen, RWTH Aachen, 52057, Aachen, Germany

    Klaus Zerres

  4. Department of Plastic Surgery and Hand Surgery, Burn Center, University Hospital of Aachen, RWTH Aachen, 52057, Aachen, Germany

    Seth Woodruff

  5. Clinic for Cardiac Surgery, University Hospital of Aachen, RWTH Aachen, 52057, Aachen, Germany

    Georg Langebartels

  6. Institute of Pharmacology, University Hospital of Hamburg, Hamburg, Germany

    Thomas Rau

  7. Interdisciplinary Intermediate Care, University Hospital of Aachen, Pauwelsstrasse30, 52057, Aachen, Germany

    Jan R. Ortlepp

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  1. Cordula Meyer zu Schwabedissen
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  2. Vera Mevissen
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  9. Jan R. Ortlepp
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Correspondence to Jan R. Ortlepp.

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Schwabedissen, C.M.z., Mevissen, V., Schmitz, F. et al. Obesity is associated with a slower response to initial phenprocoumon therapy whereas CYP2C9 genotypes are not. Eur J Clin Pharmacol 62, 713–720 (2006). https://doi.org/10.1007/s00228-006-0158-3

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  • DOI: https://doi.org/10.1007/s00228-006-0158-3

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