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

• DOI: 10.1371/journal.pone.0041360
• Publication Date: 2012-07-21T08:36:13Z
• Authors: Alberto M. Borobia; Rubin Lubomirov; Elena Ramírez; Alicia Lorenzo; Armando Campos; Raul Muñoz-Romo; Carmen Fernández-...; Jesús Frías; Antonio J. Carcas
• Keywords: Acenocoumarol; VKORC1; Concomitant

Appropriate dosing of coumarins is difficult to establish, due significant inter-individual variability in the dose required obtain stable anticoagulation. Several genetic and other clinical factors have been associated with dose, some pharmacogenetic-guided algorithms for warfarin acenocoumarol developed mixed populations. We recruited 147 patients thromboembolic disease who were on doses an international normalized ratio (INR) between 2 3. ascertained influence variables by multiple linear regression analysis a derivation cohort (DC; n = 117) algorithm that included (age, body mass index concomitant drugs) variations VKORC1, CYP2C9, CYP4F2 APOE. For purposes comparison, model including only data was created. The explained 22% variability, which increased 60.6% when pharmacogenetic information (p<0.001); APOE variants 4.9% this variability. mean absolute error predicted (mg/week) obtained 3.63 vs. 5.08 mg/week (95% CI: 0.88 2.04). In testing (n 30), mere 7% compared 39% algorithm. Considering more clinically relevant parameter, correctly real 59.8% cases (DC) 37.6% 10 35). Therefore number needed genotype avoid one over- or under-dosing estimated be 5.