title: Application of Akaike information criterion to evaluate warfarin dosing algorithm.
abstract: BACKGROUND
  Several factors responsible for inter-individual differences in response to warfarin have been confirmed; however, unidentified factors appear to remain. The purpose of this study was to examine a simple method to evaluate whether optional variables are appropriate as factors to improve dosing algorithms.
  
  
  METHODS
  All patients were Japanese. Genotyping of selected genes was conducted, and other information was obtained from medical record. Dosing algorithms were constructed by multivariate linear regression analyses and were evaluated by the Akaike Information Criterion (AIC).
  
  
  CONCLUSIONS
  Multivariate analysis showed that white blood-cell count (WBC), concomitant use of allopurinol, and CYP4F2 genotype are apparently involved in warfarin dose variation, in addition to well-known factors, such as age and VKORC1 genotype. We evaluated the adequacy of these variables as factors to improve the dosing algorithm using the AIC. Addition of WBC, allopurinol administration and CYP4F2 genotype to the basal algorithm resulted in decreased AIC, suggesting that these factor candidates may contribute to improving the prediction of warfarin maintenance dose. This study is the first to evaluate the warfarin dosing algorithm by AIC. To further improve the dosing algorithm, AIC may be a simple and useful tool to evaluate both the model itself and factors to be incorporated into the algorithm.
authors.affiliation: Laboratory of Clinical Pharmacology, Graduate School of Pharmaceutical Sciences, Chiba University, University Hospital, Department of Cardiovascular Surgery, Chiba, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Harada
authors.forename: Noritaka
authors.initials: N
authors.lastname: Ariyoshi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Shimura
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Sato
authors.forename: Iichiro
authors.initials: I
authors.lastname: Yokoyama
authors.forename: Kaori
authors.initials: K
authors.lastname: Takahashi
authors.forename: Shin-ichi
authors.initials: S
authors.lastname: Yamagata
authors.forename: Mizuho
authors.initials: M
authors.lastname: Imamaki
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Kobayashi
authors.forename: Itsuko
authors.initials: I
authors.lastname: Ishii
authors.forename: Masaru
authors.initials: M
authors.lastname: Miyazaki
authors.forename: Mitsukazu
authors.initials: M
authors.lastname: Kitada
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000493:Allopurinol / Q000008:administration & dosage; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D001777:Blood Coagulation / Q000187:drug effects*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D000072470:Cytochrome P450 Family 4; D054796:Drug Dosage Calculations; D005260:Female; D005838:Genotype; D006801:Humans; D007564:Japan; D007958:Leukocyte Count; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D006899:Mixed Function Oxygenases / Q000235:genetics; D015999:Multivariate Analysis; D010597:Pharmacogenetics; D010641:Phenotype; D064417:Vitamin K Epoxide Reductases; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics
chemical_list: D000925:Anticoagulants; D014859:Warfarin; D000493:Allopurinol; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human; C578523:VKORC1 protein, human; D064417:Vitamin K Epoxide Reductases