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An Acenocoumarol Dosing Algorithm Using Clinical and Pharmacogenetic Data in Spanish Patients with Thromboembolic Disease

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Listed:
  • Alberto M Borobia
  • Rubin Lubomirov
  • Elena Ramírez
  • Alicia Lorenzo
  • Armando Campos
  • Raul Muñoz-Romo
  • Carmen Fernández-Capitán
  • Jesús Frías
  • Antonio J Carcas

Abstract

Appropriate dosing of coumarins is difficult to establish, due to significant inter-individual variability in the dose required to obtain stable anticoagulation. Several genetic and other clinical factors have been associated with the coumarins dose, and some pharmacogenetic-guided dosing algorithms for warfarin and acenocoumarol have been developed for mixed populations. We recruited 147 patients with thromboembolic disease who were on stable doses and with an international normalized ratio (INR) between 2 and 3. We ascertained the influence of clinical and genetic variables on the stable acenocoumarol dose by multiple linear regression analysis in a derivation cohort (DC; n = 117) and developed an algorithm for dosing that included clinical factors (age, body mass index and concomitant drugs) and genetic variations of VKORC1, CYP2C9, CYP4F2 and APOE. For purposes of comparison, a model including only clinical data was created. The clinical factors explained 22% of the dose variability, which increased to 60.6% when pharmacogenetic information was included (p

Suggested Citation

  • Alberto M Borobia & Rubin Lubomirov & Elena Ramírez & Alicia Lorenzo & Armando Campos & Raul Muñoz-Romo & Carmen Fernández-Capitán & Jesús Frías & Antonio J Carcas, 2012. "An Acenocoumarol Dosing Algorithm Using Clinical and Pharmacogenetic Data in Spanish Patients with Thromboembolic Disease," PLOS ONE, Public Library of Science, vol. 7(7), pages 1-10, July.
    • Handle: RePEc:plo:pone00:0041360
    DOI: 10.1371/journal.pone.0041360
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