The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements:: proposal for a new dosing regimen
The impact of CYP2C9 and VKORC1 genetic polymorphism and patient characteristics upon warfarin dose requirements:: proposal for a new dosing regimen
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DOI：
10.1182/blood-2005-03-1108
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发表时间：
2005-10-01
期刊：
影响因子：
20.3
通讯作者：
Kamali, F
中科院分区：
文献类型：
--
作者：
Sconce, EA;Khan, TI;Kamali, F
目前的给药算法没有考虑华法林剂量确定的遗传和环境因素。本研究调查了年龄、CYP 2C 9和VKORC 1基因型以及体型对华法林剂量需求的影响。研究了297名稳定抗凝的患者，目标国际标准化比值（INR）为2.0至3.0。对CYP 2C 9（*2和 *3等位基因）和VKORC 1（-1639多态性）进行遗传分析，并测定静脉INR和血浆R-和S-华法林浓度。CYP 2C 9纯合子野生型患者的平均华法林日剂量需求量最高，与携带变异 *2和 *3等位基因的患者相比（P
Current dosing algorithms do not account for genetic and environmental factors for warfarin dose determinations. This study investigated the contribution of age, CYP2C9 and VKORC1 genotype, and body size to warfarin-dose requirements. Studied were 297 patents with stable anticoagulation with a target international normalized ratio (INR) of 2.0 to 3.0. Genetic analyses for CYP2C9 (*2 and *3 alleles) and VKORC1 (- 1639 polymorphism) were performed and venous INR and plasma R- and S-warfarin concentrations determined. The mean warfarin daily dose requirement was highest in CYP2C9 homozygous wild-type patients, compared with those with the variant *2 and *3 alleles (P