title: VKORC1 and CYP2C9 genotypic data-based dose prediction alone does not accurately predict warfarin dose requirements in some Malaysian patients.
abstract: OBJECTIVE
  VKORC1 and CYP2C9 genetic polymorphisms may not accurately predict warfarin dose requirements. We evaluated an existing warfarin dosing algorithm developed for Malaysian patients that was based only on VKORC1 and CYP2C9 genes.
  
  
  METHODS
  Five Malay patients receiving warfarin maintenance therapy were investigated for their CYP2C9*2, CYP2C9*3, and VKORC1-1639G>A genotypes and their vitamin K-dependent (VKD) clotting factor activities. The records of their daily warfarin doses and international normalized ratio (INR) 2 years prior to and after the measurement of VKD clotting factors activities were acquired. The mean warfarin doses were compared with predicted warfarin doses calculated from a genotypic-based dosing model developed for Asians.
  
  
  RESULTS
  A patient with the VKORC1-1639 GA genotype, who was supposed to have higher dose requirements, had a lower mean warfarin dose similar to those having the VKORC1-1639 AA genotype. This discrepancy may be due to the coadministration of celecoxib, which has the potential to decrease warfarins metabolism. Not all patients' predicted mean warfarin doses based on a previously developed dosing algorithm for Asians were similar to the actual mean warfarin dose, with the worst predicted dose being 54.34% higher than the required warfarin dose.
  
  
  CONCLUSIONS
  Multiple clinical factors can significantly change the actual required dose from the predicted dose from time to time. The additions of other dynamic variables, especially INR, VKD clotting factors, and concomitant drug use, into the dosing model are important in order to improve its accuracy.
authors.forename: Yung An
authors.initials: YA
authors.lastname: Chua
authors.forename: Wan Zaidah
authors.initials: WZ
authors.lastname: Abdullah
authors.forename: Zurkurnai
authors.initials: Z
authors.lastname: Yusof
authors.forename: Siew Hua
authors.initials: SH
authors.lastname: Gan
mesh_terms: D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics; D044466:Asian People / Q000235:genetics; D001777:Blood Coagulation / Q000235:genetics; D001778:Blood Coagulation Disorders / Q000188:drug therapy / Q000235:genetics; D065729:Cytochrome P-450 CYP2C9 / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D016903:Drug Monitoring; D005260:Female; D006801:Humans; D019934:International Normalized Ratio; D008296:Malaysia; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D011110:Polymorphism, Genetic; D013927:Thrombosis / Q000188:drug therapy / Q000235:genetics; D064417:Vitamin K Epoxide Reductases / Q000235:genetics*; D014859:Warfarin / Q000008:administration & dosage / Q000493:pharmacokinetics
chemical_list: D000925:Anticoagulants; D014859:Warfarin; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases