title: Development of a pharmacogenetic-guided warfarin dosing algorithm for Puerto Rican patients.
abstract: OBJECTIVE
  This study was aimed at developing a pharmacogenetic-driven warfarin-dosing algorithm in 163 admixed Puerto Rican patients on stable warfarin therapy.
  
  
  METHODS
  A multiple linear-regression analysis was performed using log-transformed effective warfarin dose as the dependent variable, and combining CYP2C9 and VKORC1 genotyping with other relevant nongenetic clinical and demographic factors as independent predictors.
  
  
  RESULTS
  The model explained more than two-thirds of the observed variance in the warfarin dose among Puerto Ricans, and also produced significantly better 'ideal dose' estimates than two pharmacogenetic models and clinical algorithms published previously, with the greatest benefit seen in patients ultimately requiring <7 mg/day. We also assessed the clinical validity of the model using an independent validation cohort of 55 Puerto Rican patients from Hartford, CT, USA (R(2) = 51%).
  
  
  CONCLUSIONS
  Our findings provide the basis for planning prospective pharmacogenetic studies to demonstrate the clinical utility of genotyping warfarin-treated Puerto Rican patients.
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, University of Puerto Rico, Room 420, PO Box 365067, San Juan, PR 00936-5067, USA.
authors.forename: Alga S
authors.initials: AS
authors.lastname: Ramos
authors.forename: Richard L
authors.initials: RL
authors.lastname: Seip
authors.forename: Giselle
authors.initials: G
authors.lastname: Rivera-Miranda
authors.forename: Marcos E
authors.initials: ME
authors.lastname: Felici-Giovanini
authors.forename: Rafael
authors.initials: R
authors.lastname: Garcia-Berdecia
authors.forename: Yirelia
authors.initials: Y
authors.lastname: Alejandro-Cowan
authors.forename: Mohan
authors.initials: M
authors.lastname: Kocherla
authors.forename: Iadelisse
authors.initials: I
authors.lastname: Cruz
authors.forename: Juan F
authors.initials: JF
authors.lastname: Feliu
authors.forename: Carmen L
authors.initials: CL
authors.lastname: Cadilla
authors.forename: Jessica Y
authors.initials: JY
authors.lastname: Renta
authors.forename: Krystyna
authors.initials: K
authors.lastname: Gorowski
authors.forename: Cunegundo
authors.initials: C
authors.lastname: Vergara
authors.forename: Gualberto
authors.initials: G
authors.lastname: Ruaño
authors.forename: Jorge
authors.initials: J
authors.lastname: Duconge
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000925:Anticoagulants / Q000008:administration & dosage; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D065729:Cytochrome P-450 CYP2C9; D004305:Dose-Response Relationship, Drug; D005260:Female; D006630:Hispanic or Latino; D006801:Humans; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics*; D011446:Prospective Studies; D012044:Regression Analysis; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage*
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D006899:Mixed Function Oxygenases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases