title: VKORC1, CYP2C9 and CYP4F2 genetic-based algorithm for warfarin dosing: an Italian retrospective study.
abstract: OBJECTIVE
  A total of 371 patients under stable warfarin therapy were retrospectively selected to develop a pharmacogenetic algorithm to identify the individual maintenance dose.
  
  
  METHODS
  The variables that were entered into the algorithm were: VKORC1, CYP2C9 and CYP4F2 polymorphisms, body surface area and age.
  
  
  RESULTS
  The percentage of cases whose predicted mean weekly warfarin dose was within 20% of the actual maintenance dose was 51.8% considering patients overall, and were 36.2, 66.2 and 55.4%, respectively, taking into account patients requiring low (≤25 mg/week), intermediate (25-45 mg/week) and high (≥45 mg/week) doses. The algorithm could correctly assign 73.8 and 63.2% of patients to the low- and high-dose regimens, respectively. We developed and validated a pharmacogenetic algorithm in a series of Italian patients, we then tested, in the same series of italian patients, the formulas of three published algorithms. These three algorithms were developed and validated by their authors in a series of patients different from our own. The performance of our algorithm in our patients series was slightly higher than that achieved when using the three other algorithms in our patients series.
  
  
  CONCLUSIONS
  The high predictive accuracy of low and high warfarin requirements of our algorithm warrants its application in prospective studies for clinical validation.
authors.affiliation: Department of Laboratory Medicine, University-Hospital of Padua, 35128 Padua, Italy.
authors.forename: Carlo-Federico
authors.initials: CF
authors.lastname: Zambon
authors.forename: Vittorio
authors.initials: V
authors.lastname: Pengo
authors.forename: Roberto
authors.initials: R
authors.lastname: Padrini
authors.forename: Daniela
authors.initials: D
authors.lastname: Basso
authors.forename: Stefania
authors.initials: S
authors.lastname: Schiavon
authors.forename: Paola
authors.initials: P
authors.lastname: Fogar
authors.forename: Alessandra
authors.initials: A
authors.lastname: Nisi
authors.forename: Anna Chiara
authors.initials: AC
authors.lastname: Frigo
authors.forename: Stefania
authors.initials: S
authors.lastname: Moz
authors.forename: Michela
authors.initials: M
authors.lastname: Pelloso
authors.forename: Mario
authors.initials: M
authors.lastname: Plebani
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D001777:Blood Coagulation / Q000187:drug effects / Q000235:genetics; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics*; D000072470:Cytochrome P450 Family 4; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D057285:Precision Medicine; D012189:Retrospective Studies; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D014859:Warfarin; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases