title: Prediction of stable acenocoumarol dose by a pharmacogenetic algorithm.
abstract: OBJECTIVE
  To develop an acenocoumarol (ACN) dosing algorithm for patients with atrial fibrillation or venous thromboembolism, considering the influence on the stable ACN dose of clinical factors and gene polymorphisms, including CYP2C9*2/*3, VKORC1, CYP4F2*3, ABCB1, APOE, CYP2C19*2/*17, and GGCX.
  
  
  RESULTS
  A retrospective observational study was carried out to obtain clinical and pharmacogenetic dose algorithms by multiple linear regression of results in a cohort of 134 patients under treatment with a stable ACN dose for atrial fibrillation or venous thromboembolism and to test them in an independent validation cohort of 30 patients.The pharmacogenetic dosing algorithm included CYP2C9, VKORC1, and APOE, which explained 56.6% of the variability in the stable ACN dose. Lower deviation from the stable dose and increased accuracy were shown by the pharmacogenetic algorithm, which correctly classified 67% of patients with a deviation of up to 20%.
  
  
  CONCLUSIONS
  The variability in the stable ACN dose was better explained by a pharmacogenetic algorithm including clinical and genetic factors (CYP2C9, VKORC1, and APOE) than by a clinical algorithm, providing a more accurate dosage prediction.
authors.affiliation: aPharmacogenetics Unit, UGC Provincial de Farmacia de Granada, Instituto de Investigación Biosanitaria de Granada, Hospitales Universitarios de Granada Avda. Fuerzas Armadas, 2 bHaematology Department, Complejo Hospitalario de Granada cDepartment of Pharmacology, Faculty of Pharmacy, University of Granada, Campus Universitario de Cartuja, Granada, Spain.
authors.forename: Enrique
authors.initials: E
authors.lastname: Jiménez-Varo
authors.forename: Marisa
authors.initials: M
authors.lastname: Cañadas-Garre
authors.forename: María J
authors.initials: MJ
authors.lastname: Gutiérrez-Pimentel
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Calleja-Hernández
mesh_terms: D000074:Acenocoumarol / Q000008:administration & dosage*; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000925:Anticoagulants / Q000008:administration & dosage*; D001057:Apolipoproteins E / Q000235:genetics; D001281:Atrial Fibrillation / Q000188:drug therapy; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics; D054796:Drug Dosage Calculations; D005260:Female; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics / Q000379:methods*; D012189:Retrospective Studies; D054556:Venous Thromboembolism / Q000188:drug therapy; D064417:Vitamin K Epoxide Reductases / Q000235:genetics
chemical_list: D000925:Anticoagulants; D001057:Apolipoproteins E; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases; D000074:Acenocoumarol