Aomori T, Obayashi K, Fujita Y, Araki T, Nakamura K, Nakamura T, Kurabayashi M, Yamamoto K
Department of Pharmacy, Gunma University Hospital, Maebashi, Japan.
Pharmazie. 2011 Mar;66(3):222-5.
Polymorphisms in cytochrome P450 (CYP) 2C9 and the vitamin K oxide reductase complex subunit 1 (VKORC1) greatly affect the maintenance dose of warfarin. To prevent adverse events, immediate dose adjustment is required. The purpose of this study was to investigate the influence of these polymorphisms on the time taken to determine the warfarin maintenance dose for individual patients, and to assess the advantages of genotype-based dosing on initial anticoagulant therapy. We analyzed the genotypes of CYP2C9 and VKORC1 from 72 patients. The number of days taken to determine the maintenance dose was compared with the genotypes. The time taken to determine the maintenance dose of warfarin in group A (CYP2C9*1/*1, VKORC1 -1639AA), B (*1/*1, - 1639GA), C (*1/*3, - 1639AA), and D (*1/*3, - 1639GA) patients was 19 +/- 19, 28 +/- 28, 27 +/- 20 and 7 days, respectively. We analyzed the relationship between the initial dose of warfarin and the number of days required to determine the maintenance dose based on the VKORC1 genotypes. Patients with the VKORC1 - 1639AA genotype and who were initially treated with more than 3mg warfarin, required approximately 2 weeks for the maintenance dose to be determined. Patients with the VKORC1 - 1639GA genotype and the same initial warfarin dosage required approximately a month; however, patients initially treated with 5 mg of warfarin only required 9.5 +/- 5.3 days. We found a tendency that the time taken to determine the warfarin maintenance dose depends on the genotypes. Genotype-based dosing may improve initial anticoagulant therapy.
细胞色素P450（CYP）2C9和维生素K氧化还原酶复合体亚基1（VKORC1）的多态性极大地影响华法林的维持剂量。为预防不良事件，需要立即调整剂量。本研究的目的是调查这些多态性对个体患者确定华法林维持剂量所需时间的影响，并评估基于基因型给药在初始抗凝治疗中的优势。我们分析了72例患者的CYP2C9和VKORC1基因型。将确定维持剂量所需的天数与基因型进行比较。A组（CYP2C9*1/*1，VKORC1 -1639AA）、B组（*1/*1，-1639GA）、C组（*1/*3，-1639AA）和D组（*1/*3，-1639GA）患者确定华法林维持剂量所需的时间分别为19±19天、28±28天、27±20天和7天。我们分析了华法林初始剂量与基于VKORC1基因型确定维持剂量所需天数之间的关系。VKORC1 -1639AA基因型且初始接受超过3mg华法林治疗的患者，确定维持剂量大约需要2周时间。具有VKORC1 -1639GA基因型且初始华法林剂量相同的患者大约需要1个月时间；然而，初始接受5mg华法林治疗的患者仅需要9.5±5.3天。我们发现确定华法林维持剂量所需时间存在取决于基因型的趋势。基于基因型给药可能会改善初始抗凝治疗。
