TY - JOUR
T1 - Effect of the VKORC1 genotype on warfarin dose requirements in Japanese pediatric patients
AU - Kato, Yuya
AU - Ichida, Fukiko
AU - Saito, Kazuyoshi
AU - Watanabe, Kazuhiro
AU - Hirono, Keiichi
AU - Miyawaki, Toshio
AU - Yoshimura, Naoki
AU - Horiuchi, Isao
AU - Taguchi, Masato
AU - Hashimoto, Yukiya
N1 - Funding Information:
Acknowledgments: This work was supported in part by Grants-in-Aid for Scientific Research from the Japan Society for the Promotion of Sciences ¤JSPS¥, from the Ministry of Education, Culture, Sports, Science and Technology ¤MEXT¥, and the Japan Research Foundation for Clinical Pharmacology.
PY - 2011
Y1 - 2011
N2 - The primary aim of the present study was to evaluate the effect of the genotype of vitamin K epoxide reductase complex 1 (VKORC1) on warfarin dose requirements in Japanese pediatric patients. Forty-eight pediatric patients (0.4219.25 years old) in whom stable anticoagulation was achieved by warfarin were enrolled in this study, and the polymorphic alleles of VKORC1 and CYP2C9 were determined for each subject. The relative impact of covariates on the anticoagulant effect of warfarin was evaluated by multiple regression analysis. It was found that VKORC1 genotype and age were major factors affecting the relationship between the weight-normalized warfarin dose and the therapeutic prothrombin timeinternational normalized ratio (PT-INR). Because only one patient had the CYP2C9*3 allele, we could not evaluate the effect of CYP2C9 polymorphisms on the anticoagulant effect of warfarin. In contrast, the anticoagulant effect of warfarin in patients with the VKORC1 1173CT or 1173CC genotype was 52.3% of that in patients with the 1173TT genotype. In addition, the anticoagulant effect of warfarin was shown to increase by 10.5% per year in Japanese pediatric patients. In conclusion, genotyping of VKORC1 will be useful in establishing individual anticoagulant therapy with warfarin, and it should be noted that a higher weight-normalized dose of warfarin is required in younger pediatric patients.
AB - The primary aim of the present study was to evaluate the effect of the genotype of vitamin K epoxide reductase complex 1 (VKORC1) on warfarin dose requirements in Japanese pediatric patients. Forty-eight pediatric patients (0.4219.25 years old) in whom stable anticoagulation was achieved by warfarin were enrolled in this study, and the polymorphic alleles of VKORC1 and CYP2C9 were determined for each subject. The relative impact of covariates on the anticoagulant effect of warfarin was evaluated by multiple regression analysis. It was found that VKORC1 genotype and age were major factors affecting the relationship between the weight-normalized warfarin dose and the therapeutic prothrombin timeinternational normalized ratio (PT-INR). Because only one patient had the CYP2C9*3 allele, we could not evaluate the effect of CYP2C9 polymorphisms on the anticoagulant effect of warfarin. In contrast, the anticoagulant effect of warfarin in patients with the VKORC1 1173CT or 1173CC genotype was 52.3% of that in patients with the 1173TT genotype. In addition, the anticoagulant effect of warfarin was shown to increase by 10.5% per year in Japanese pediatric patients. In conclusion, genotyping of VKORC1 will be useful in establishing individual anticoagulant therapy with warfarin, and it should be noted that a higher weight-normalized dose of warfarin is required in younger pediatric patients.
UR - http://www.scopus.com/inward/record.url?scp=79959950122&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79959950122&partnerID=8YFLogxK
U2 - 10.2133/dmpk.DMPK-10-NT-082
DO - 10.2133/dmpk.DMPK-10-NT-082
M3 - Comment/debate
C2 - 21273734
AN - SCOPUS:79959950122
SN - 1347-4367
VL - 26
SP - 295
EP - 299
JO - Drug Metabolism and Pharmacokinetics
JF - Drug Metabolism and Pharmacokinetics
IS - 3
ER -