title: A novel acenocoumarol pharmacogenomic dosing algorithm for the Greek population of EU-PACT trial.
abstract: OBJECTIVE
  To generate and validate a pharmacogenomic-guided (PG) dosing algorithm for acenocoumarol in the Greek population. To compare its performance with other PG algorithms developed for the Greek population.
  
  
  METHODS
  A total of 140 Greek patients participants of the EU-PACT trial for acenocoumarol, a randomized clinical trial that prospectively compared the effect of a PG dosing algorithm with a clinical dosing algorithm on the percentage of time within INR therapeutic range, who reached acenocoumarol stable dose were included in the study.
  
  
  RESULTS
  CYP2C9 and VKORC1 genotypes, age and weight affected acenocoumarol dose and predicted 53.9% of its variability. EU-PACT PG algorithm overestimated acenocoumarol dose across all different CYP2C9/VKORC1 functional phenotype bins (predicted dose vs stable dose in normal responders 2.31 vs 2.00 mg/day, p = 0.028, in sensitive responders 1.72 vs 1.50 mg/day, p = 0.003, in highly sensitive responders 1.39 vs 1.00 mg/day, p = 0.029). The PG algorithm previously developed for the Greek population overestimated the dose in normal responders (2.51 vs 2.00 mg/day, p < 0.001).
  
  
  CONCLUSIONS
  Ethnic-specific dosing algorithm is suggested for better prediction of acenocoumarol dosage requirements in patients of Greek origin.
authors.affiliation: DNALEX S.A., Leontaridou 2, Alexandroupolis, Greece.
authors.forename: Georgia
authors.initials: G
authors.lastname: Ragia
authors.affiliation: Cardiology Department, Onassis Cardiac Surgery Center, Athens, Greece.
authors.forename: Vana
authors.initials: V
authors.lastname: Kolovou
authors.affiliation: Cardiology Department, Onassis Cardiac Surgery Center, Athens, Greece.
authors.forename: Genovefa
authors.initials: G
authors.lastname: Kolovou
authors.affiliation: University Cardiology Department, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Stavros
authors.initials: S
authors.lastname: Konstantinides
authors.affiliation: Second Department of Internal Medicine, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Efstratios
authors.initials: E
authors.lastname: Maltezos
authors.affiliation: Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.|Clinical Pharmacology Unit, Academic General Hospital of Evros, Alexandroupolis, Greece.
authors.forename: Anna
authors.initials: A
authors.lastname: Tavridou
authors.affiliation: University Cardiology Department, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tziakas
authors.affiliation: Division of Pharmacoepidemiology & Clinical Pharmacology, Department of Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
authors.forename: Anke H
authors.initials: AH
authors.lastname: Maitland-van der Zee
authors.affiliation: Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece.|Clinical Pharmacology Unit, Academic General Hospital of Evros, Alexandroupolis, Greece.
authors.forename: Vangelis G
authors.initials: VG
authors.lastname: Manolopoulos
mesh_terms: D000074:Acenocoumarol / Q000008:administration & dosage*; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000925:Anticoagulants / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005062:European Union; D005260:Female; D005500:Follow-Up Studies; D006115:Greece / Q000208:ethnology; D006801:Humans; D008297:Male; D010597:Pharmacogenetics / Q000379:methods*; D011159:Population Surveillance / Q000379:methods; D011446:Prospective Studies; D016037:Single-Blind Method; D014812:Vitamin K / Q000037:antagonists & inhibitors
chemical_list: D000925:Anticoagulants; D014812:Vitamin K; D000074:Acenocoumarol
keywords: CYP2C9; EU-PACT; Greece; VKORC1; acenocoumarol; dosing algorithm; pharmacogenomics