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The Active Metabolite of Warfarin (3'-Hydroxywarfarin) and Correlation with INR, Warfarin and Drug Weekly Dosage in Patients under Oral Anticoagulant Therapy: A Pharmacogenetics Study

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  • Donato Gemmati
  • Francesco Burini
  • Anna Talarico
  • Matteo Fabbri
  • Cesare Bertocco
  • Marco Vigliano
  • Stefano Moratelli
  • Antonio Cuneo
  • Maria Luisa Serino
  • Francesco Maria Avato
  • Veronica Tisato
  • Rosa Maria Gaudio

Abstract

Objectives: Warfarin oral anticoagulant therapy (OAT) requires regular and frequent drug adjustment monitored by INR. Interindividual variability, drug and diet interferences, and genetics (VKORC1 and CYP2C9) make the maintenance/reaching of stable INR a not so easy task. HPLC assessment of warfarin/enantiomers was suggested as a valid monitoring-tool along with INR, but definite results are still lacking. We evaluated possible correlations between INR, warfarin/3’-hydroxywarfarin, and drug weekly dosage aimed at searching novel alternatives to OAT monitoring. VKORC1/CYP2C9 pharmacogenetics investigation was performed to account for the known influence on warfarin homeostasis. Methods: 133 OAT patients were recruited and assessed for warfarin/3’-hydroxywarfarin serum levels (HPLC), INR, and VKORC1 and CYP2C9 genotypes. A subgroup of 52 patients were monitored in detail (5 consecutive controls; c0-c4) till the target INR was reached. Correlation analyses were performed in both groups Results: In the whole OAT group both warfarin and 3’-hydroxywarfarin correlate with INR at comparable degree (r2 = 0.0388 and 0.0362 respectively). Conversely, warfarin weekly dosage better correlates with warfarin than with 3’-hydroxywarfarin (r2 = 0.0975 and r2 = 0.0381 respectively), but considering together warfarin plus 3’-hydroxywarfarin the correlation strongly increased (r2 = 0.1114; p

Suggested Citation

  • Donato Gemmati & Francesco Burini & Anna Talarico & Matteo Fabbri & Cesare Bertocco & Marco Vigliano & Stefano Moratelli & Antonio Cuneo & Maria Luisa Serino & Francesco Maria Avato & Veronica Tisato , 2016. "The Active Metabolite of Warfarin (3'-Hydroxywarfarin) and Correlation with INR, Warfarin and Drug Weekly Dosage in Patients under Oral Anticoagulant Therapy: A Pharmacogenetics Study," PLOS ONE, Public Library of Science, vol. 11(9), pages 1-16, September.
    • Handle: RePEc:plo:pone00:0162084
    DOI: 10.1371/journal.pone.0162084
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    References listed on IDEAS

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    1. Andrea L Jorgensen & Richard J FitzGerald & James Oyee & Munir Pirmohamed & Paula R Williamson, 2012. "Influence of CYP2C9 and VKORC1 on Patient Response to Warfarin: A Systematic Review and Meta-Analysis," PLOS ONE, Public Library of Science, vol. 7(8), pages 1-1, August.
    2. Cristina Mazzaccara & Valeria Conti & Rosario Liguori & Vittorio Simeon & Mario Toriello & Angelo Severini & Corrado Perricone & Alfonso Meccariello & Pasquale Meccariello & Dino Franco Vitale & Ameli, 2013. "Warfarin Anticoagulant Therapy: A Southern Italy Pharmacogenetics-Based Dosing Model," PLOS ONE, Public Library of Science, vol. 8(8), pages 1-8, August.
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