Department of Laboratory Medicine, Konyang University Hospital, College of Medical Science Konyang University, Daejon, Korea.
Clin Ther. 2011 Oct;33(10):1371-80. doi: 10.1016/j.clinthera.2011.09.004. Epub 2011 Oct 6.
The pharmacokinetics and pharmacodynamics of warfarin are affected by polymorphisms in the genes coding for cytochrome P450 2C9 (CYP2C9) and vitamin K epoxide reductase complex subunit 1 (VKORC1).
The objective of this study was to develop a pharmacogenetic dosing algorithm for warfarin in Korean patients with atrial fibrillation and to compare it with the published pharmacogenetic dosing algorithms for accuracy to predict warfarin maintenance dose.
Clinical and genetic data from 130 Korean patients with atrial fibrillation (mean [SD] age: 66.2 [13.3] years; gender, male/female: 86/44; mean body weight: 66.6 [11.6] kg) were used to create a dosing algorithm, which was validated against an independent group of patients (n = 108; mean age: 67.4 [10.1] years; gender, male/female: 69/39; mean body weight: 66.0 [10.9] kg). Validation cohort data for the 12 previously published dosing algorithms incorporating CYP2C9 and VKORC1 genotype information were also applied.
A multivariate regression model including the variables of age, VKORC1 and CYP2C9 genotype, body surface area, and statin status produced the best model for estimating the warfarin dose (R(2) = 0.62). Among the 12 algorithms that were compared, the predicted doses using algorithms derived from both the Swedish Warfarin Genetics (WARG) study and the Korean population study showed the best correlation with actual warfarin doses. Comparing the percentage of patients whose predicted dosages were within 20% of actual dosages, these algorithms showed similar overall performance.
This study derived and validated a multivariate regression model for daily warfarin dose requirements in Korean patients with atrial fibrillation. As no algorithm could be considered the best for all dosing ranges, it may be important to consider the characteristics or limitations of each dosing algorithm and the nature of a population in choosing the most appropriate pharmacogenetic dosing.
华法林的药代动力学和药效学受细胞色素 P450 2C9（CYP2C9）和维生素 K 环氧化物还原酶复合物亚基 1（VKORC1）基因编码的多态性影响。
本研究旨在为韩国心房颤动患者开发华法林的遗传药理学剂量算法，并与已发表的遗传药理学剂量算法进行比较，以评估其预测华法林维持剂量的准确性。
使用来自 130 例韩国心房颤动患者（平均[标准差]年龄：66.2[13.3]岁；性别，男/女：86/44；平均体重：66.6[11.6]kg）的临床和遗传数据来创建一个剂量算法，并将其与独立患者组（n=108；平均年龄：67.4[10.1]岁；性别，男/女：69/39；平均体重：66.0[10.9]kg）进行验证。还应用了纳入 CYP2C9 和 VKORC1 基因型信息的 12 种先前发表的剂量算法的验证队列数据。
包括年龄、VKORC1 和 CYP2C9 基因型、体表面积和他汀类药物状态等变量的多元回归模型，可最佳地预测华法林剂量（R2=0.62）。在比较的 12 种算法中，来自瑞典华法林遗传学（WARG）研究和韩国人群研究的算法所预测的剂量与实际华法林剂量相关性最好。比较预测剂量与实际剂量相差 20%以内的患者比例，这些算法的总体性能相似。
本研究为韩国心房颤动患者推导并验证了华法林每日剂量需求的多元回归模型。由于没有一种算法可以被认为适用于所有剂量范围，因此在选择最合适的遗传药理学剂量时，考虑每种剂量算法的特点或局限性以及人群的性质可能很重要。
