title: Development and comparison of a warfarin-dosing algorithm for Korean patients with atrial fibrillation.
abstract: BACKGROUND
  The pharmacokinetics and pharmacodynamics of warfarin are affected by polymorphisms in the genes coding for cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1).
  
  
  OBJECTIVE
  The objective of this study was to develop a pharmacogenetic dosing algorithm for warfarin in Korean patients with atrial fibrillation and to compare it with the published pharmacogenetic dosing algorithms for accuracy to predict warfarin maintenance dose.
  
  
  METHODS
  Clinical and genetic data from 130 Korean patients with atrial fibrillation (mean [SD] age: 66.2 [13.3] years; gender, male/female: 86/44; mean body weight: 66.6 [11.6] kg) were used to create a dosing algorithm, which was validated against an independent group of patients (n = 108; mean age: 67.4 [10.1] years; gender, male/female: 69/39; mean body weight: 66.0 [10.9] kg). Validation cohort data for the 12 previously published dosing algorithms incorporating CYP2C9 and VKORC1 genotype information were also applied.
  
  
  RESULTS
  A multivariate regression model including the variables of age, VKORC1 and CYP2C9 genotype, body surface area, and statin status produced the best model for estimating the warfarin dose (R(2) = 0.62). Among the 12 algorithms that were compared, the predicted doses using algorithms derived from both the Swedish Warfarin Genetics (WARG) study and the Korean population study showed the best correlation with actual warfarin doses. Comparing the percentage of patients whose predicted dosages were within 20% of actual dosages, these algorithms showed similar overall performance.
  
  
  CONCLUSIONS
  This study derived and validated a multivariate regression model for daily warfarin dose requirements in Korean patients with atrial fibrillation. As no algorithm could be considered the best for all dosing ranges, it may be important to consider the characteristics or limitations of each dosing algorithm and the nature of a population in choosing the most appropriate pharmacogenetic dosing.
authors: Department of Laboratory Medicine, Konyang University Hospital, College of Medical Science Konyang University, Daejon, Korea.
authors: Hyun-Jung
authors: HJ
authors: Cho
authors: Young-Keun
authors: YK
authors: On
authors: Oh Young
authors: OY
authors: Bang
authors: Jong-Won
authors: JW
authors: Kim
authors: Wooseong
authors: W
authors: Huh
authors: Jae-Wook
authors: JW
authors: Ko
authors: June Soo
authors: JS
authors: Kim
authors: Soo-Youn
authors: SY
authors: Lee
mesh_terms: D000368:Aged; D000465:Algorithms; D000925:Anticoagulants / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001281:Atrial Fibrillation / Q000097:blood / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D015331:Cohort Studies; D065729:Cytochrome P-450 CYP2C9; D004334:Drug Administration Schedule; D005260:Female; D005838:Genotype; D006801:Humans; D008658:Inactivation, Metabolic; D019934:International Normalized Ratio; D008297:Male; D006899:Mixed Function Oxygenases / Q000235:genetics; D015999:Multivariate Analysis; D010597:Pharmacogenetics; D012044:Regression Analysis; D056910:Republic of Korea; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000627:therapeutic use
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