title: Extrapolation of acenocoumarol pharmacogenetic algorithms.
abstract: BACKGROUND
  Acenocoumarol (ACN) has a narrow therapeutic range that is especially difficult to control at the start of its administration. Various dosing pharmacogenetic-guided dosing algorithms have been developed, but further work on their external validation is required. The aim of this study was to evaluate the extrapolation of pharmacogenetic algorithms for ACN as an alternative to the development of a specific algorithm for a given population.
  
  
  METHODS
  The predictive performance, deviation, accuracy, and clinical significance of five pharmacogenetic algorithms (EU-PACT, Borobia, Rathore, Markatos, Krishna Kumar) were compared in 189 stable ACN patients representing all indications for anticoagulant treatment.
  
  
  RESULTS
  The correlation between the dose predictions of the five pharmacogenetic models ranged from 7.7 to 70.6% and the percentage of patients with a correct prediction (deviation ≤20% from actual ACN dose) ranged from 5.9 to 40.7%. EU-PACT and Borobia pharmacogenetic dosing algorithms were the most accurate in our setting and evidenced the best clinical performance.
  
  
  CONCLUSIONS
  Among the five models studied, the EU-PACT and Borobia pharmacogenetic dosing algorithms demonstrated the best potential for extrapolation.
authors.affiliation: Pharmacogenetics Unit, UGC Provincial de Farmacia de Granada, Instituto de Investigación Biosanitaria de Granada, Complejo Hospitalario Universitario de Granada, Avda. Fuerzas Armadas, 2, 18014 Granada, Spain. Electronic address: ejimenezvaro@gmail.com.
authors.forename: Enrique
authors.initials: E
authors.lastname: Jiménez-Varo
authors.affiliation: Pharmacogenetics Unit, UGC Provincial de Farmacia de Granada, Instituto de Investigación Biosanitaria de Granada, Complejo Hospitalario Universitario de Granada, Avda. Fuerzas Armadas, 2, 18014 Granada, Spain. Electronic address: marisacgarre@gmail.com.
authors.forename: Marisa
authors.initials: M
authors.lastname: Cañadas-Garre
authors.affiliation: Pharmacogenetics Unit, UGC Provincial de Farmacia de Granada, Instituto de Investigación Biosanitaria de Granada, Complejo Hospitalario Universitario de Granada, Avda. Fuerzas Armadas, 2, 18014 Granada, Spain. Electronic address: vigaro89@gmail.com.
authors.forename: Víctor
authors.initials: V
authors.lastname: Garcés-Robles
authors.affiliation: Haematology Department, Complejo Hospitalario Universitario de Granada, Avda. Fuerzas Armadas, 2, 18014 Granada, Spain. Electronic address: mjgutierrezpimentel@yahoo.es.
authors.forename: María José
authors.initials: MJ
authors.lastname: Gutiérrez-Pimentel
authors.affiliation: Pharmacogenetics Unit, UGC Provincial de Farmacia de Granada, Instituto de Investigación Biosanitaria de Granada, Complejo Hospitalario Universitario de Granada, Avda. Fuerzas Armadas, 2, 18014 Granada, Spain. Electronic address: mangel.calleja.exts@juntadeandalucia.es.
authors.forename: Miguel Ángel
authors.initials: MÁ
authors.lastname: Calleja-Hernández
mesh_terms: D000074:Acenocoumarol / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000925:Anticoagulants / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics / Q000379:methods
chemical_list: D000925:Anticoagulants; D000074:Acenocoumarol
keywords: Acenocoumarol; Dosing algorithms; Extrapolation; Pharmacogenetics; VKORC1