Application of Akaike information criterion to evaluate warfarin dosing algorithm

• Published in: Thrombosis research Vol. 126; no. 3; pp. 183 - 190
• Main Authors: Harada, Takumi, Ariyoshi, Noritaka, Shimura, Hitoshi, Sato, Yasunori, Yokoyama, Iichiro, Takahashi, Kaori, Yamagata, Shin-ichi, Imamaki, Mizuho, Kobayashi, Yoshio, Ishii, Itsuko, Miyazaki, Masaru, Kitada, Mitsukazu
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 01.09.2010; Elsevier
• Subjects: Adult; Aged; Aged, 80 and over; AIC; Algorithms; Allopurinol - administration & dosage; Anticoagulants - administration & dosage; Anticoagulants - adverse effects; Anticoagulants - pharmacokinetics; Biological and medical sciences; Blood and lymphatic vessels; Blood Coagulation - drug effects; Brain; Cardiology. Vascular system; CYP4F2; Cytochrome P-450 Enzyme System - genetics; Cytochrome P450 Family 4; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Drug Dosage Calculations; Female; Genotype; Hematology, Oncology and Palliative Medicine; Humans; Investigative techniques of hemodynamics; Investigative techniques, diagnostic techniques (general aspects); Japan; Leukocyte Count; Linear Models; Male; Medical sciences; Middle Aged; Mixed Function Oxygenases - genetics; Multivariate Analysis; Pharmacogenetics; Phenotype; Vitamin K Epoxide Reductases; Warfarin; Warfarin - administration & dosage; Warfarin - adverse effects; Warfarin - pharmacokinetics; C-reactive protein; Scr; ALP; ALT; γ-glutamyl transpeptidase; thyroid stimulating hormone; UA; serum creatinine; vitamin K epoxide reductase complex, subunit 1; BSA; RBC; alkaline phosphatase; Hb; AIC; CYP; uric acid; VKORC1; Warfarin; body mass index; lactate dehydrogenase; TSH; AMY; calumenin; HCT; γ-glutamyl carboxylase; T-bil; PT-INR; CRP; red blood cell count; total bilirubin; intervening sequence; IVS; hematocrit; blood urea nitrogen; prothrombin time international normalized ratio; amylase; hemoglobin; LDH; deoxyribonucleic acid; total protein; alanine transaminase; PLT; WBC; BUN; Akaike Information Criterion; BMI; γ-GTP; AST; Pharmacogenetics; CYP4F2; JSNP; cytochrome P450; Algorithms; GGCX; white blood-cell count; DNA; a database of common gene variations in the Japanse population; ALB; albumin; CALU; platelet; aspartate transaminase; TP; body surface area; Antivitamin K; Coumarine derivatives; Cardiovascular disease; Anticoagulant
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2010.05.016

Abstract Introduction 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. Materials and 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). Results and 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.