title: Development and Comparison of Warfarin Dosing Algorithms in Stroke Patients.
abstract: OBJECTIVE
  The genes for cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1) have been identified as important genetic determinants of warfarin dosing and have been studied. We developed warfarin algorithm for Korean patients with stroke and compared the accuracy of warfarin dose prediction algorithms based on the pharmacogenetics.
  
  
  METHODS
  A total of 101 patients on stable maintenance dose of warfarin were enrolled. Warfarin dosing algorithm was developed using multiple linear regression analysis. The performance of all the algorithms was characterized with coefficient of determination, determined by linear regression, and the mean of percent deviation was used to predict doses from the actual dose. In addition, we compared the performance of the algorithms using percentage of predicted dose falling within ±20% of clinically observed doses and dividing the patients into a low-dose group (≤3 mg/day), an intermediate-dose group (3-7 mg/day), and high-dose group (≥7 mg/day).
  
  
  RESULTS
  A new developed algorithms including the variables of age, body weight, and CYP2C9 and VKORC1 genotype. Our algorithm accounted for 51% of variation in the warfarin stable dose, and performed best in predicting dose within 20% of actual dose and intermediate-dose group.
  
  
  CONCLUSIONS
  Our warfarin dosing algorithm may be useful for Korean patients with stroke. Further studies to elucidate clinical utility of genotype-guided dosing and find the additional genetic association are necessary.
authors.affiliation: Department of Laboratory Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Sun-Mi
authors.initials: SM
authors.lastname: Cho
authors.affiliation: Department of Neurology, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Kyung-Yul
authors.initials: KY
authors.lastname: Lee
authors.affiliation: Department of Laboratory Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.
authors.forename: Jong Rak
authors.initials: JR
authors.lastname: Choi
authors.affiliation: Department of Laboratory Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea. kal1119@yuhs.ac.
authors.forename: Kyung-A
authors.initials: KA
authors.lastname: Lee
mesh_terms: D000368:Aged; D000465:Algorithms; D000925:Anticoagulants / Q000008:administration & dosage* / Q000627:therapeutic use; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006801:Humans; D019934:International Normalized Ratio; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010597:Pharmacogenetics; D012044:Regression Analysis; D056910:Republic of Korea; D020521:Stroke / Q000188:drug therapy* / Q000208:ethnology; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*; D014859:Warfarin / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D000925:Anticoagulants; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases
keywords: CYP2C9; Korean; VKOC1; stroke; warfarin