title: Effect of impaired renal function on the maintenance dose of warfarin in Japanese patients.
abstract: BACKGROUND
  Chronic kidney disease (CKD) alters dose-effect relationship not only of drugs eliminated by the kidney but also of some drugs metabolized by the liver and not renally excreted. It is not known whether impaired renal function alters dose-effect relationship of warfarin in Asian patients. It is also unknown whether the maintenance dose of warfarin can be predicted more accurately by incorporating renal function in Asians.
  
  
  METHODS
  This was a cross-sectional study of patients receiving constant doses of warfarin who had PT-INR within 1.5-3.0 for 3 months or longer.
  
  
  RESULTS
  In a total of 137 participants, the estimated creatinine clearance (eCrCl) was 62.5±25.5 [ml/min] and the warfarin dose was 3.21±1.46 [mg/day] (both mean±standard deviation). There was a significant correlation between warfarin dose and eCrCl (p<0.0001, r(2)=0.23). In a stepwise linear regression with the maintenance dose of warfarin as the dependent variable, eCrCl as well as age, body weight, intra-individual average prothrombin time/international normalized ratio (PT-INR), and genotype of VKORC1 -1639 G>A polymorphism were chosen as independent variables. The coefficient of determination (r(2)) of this formula was 0.47. A regression equation with all the same explanatory variables except for eCrCl had an r(2) of 0.41.
  
  
  CONCLUSIONS
  The maintenance warfarin dose was positively correlated with kidney function as represented by eCrCl in Japanese patients. Incorporating eCrCl improved accuracy of predicting warfarin maintenance dose in this population.
authors.affiliation: Division of General Internal Medicine & Primary Care, Brigham and Women's Hospital, Boston, USA. Electronic address: nai807@mail.harvard.edu.
authors.forename: Naoaki
authors.initials: N
authors.lastname: Ichihara
authors.affiliation: Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Ishigami
authors.affiliation: Department of Medical Science and Cardiorenal Medicine, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Umemura
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001835:Body Weight; D003404:Creatinine / Q000378:metabolism; D003430:Cross-Sectional Studies; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006801:Humans; D019934:International Normalized Ratio; D007564:Japan; D007668:Kidney / Q000378:metabolism / Q000503:physiopathology*; D060046:Maintenance Chemotherapy; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011517:Prothrombin Time; D064417:Vitamin K Epoxide Reductases / Q000235:genetics; D014859:Warfarin / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D003404:Creatinine; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases
keywords: Dose–effect relationship; Non-renal elimination; Renal impairment; Warfarin