Development of a pharmacogenetic-based warfarin dosing algorithm and its performance in Brazilian patients: highlighting the importance of population-specific calibration
Development of a pharmacogenetic-based warfarin dosing algorithm and its performance in Brazilian patients: highlighting the importance of population-specific calibration
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DOI：
10.2217/pgs.15.48
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发表时间：
2015-01-01
期刊：
影响因子：
2.1
通讯作者：
Pereira, Alexandre Costa
中科院分区：
文献类型：
--
作者：
Junior Lima Santos, Paulo Caleb;Marcatto, Leiliane Rodrigues;Pereira, Alexandre Costa
背景：本研究的主要目的是开发一种基于药物遗传学的华法林给药算法，并在高度混合的人群中验证它。材料与方法：我们纳入了两个接受华法林治疗的患者队列(第一队列，n=832；第二队列，n=133)。结果：我们的算法获得了40%的决定系数，包括年龄、性别、体重、身高、自我声明的种族、胺碘酮的使用、酶诱导剂的使用、VKORC1型以及根据CYP2C9基因多态预测的表型。结论：数据表明，当应用程序集中在巴西人群中的患者时，我们开发的算法比IWPC算法更准确。与目前可用的通用剂量算法相比，华法林剂量算法的群体特定推导和/或校准可以导致改进的性能。
Background: The main aims of the present study were to develop a pharmacogenetic-based warfarin dosing algorithm and to validate it in a highly admixed population. Materials & methods: We included two patient cohorts treated with warfarin (first cohort, n = 832; and second cohort, n = 133). Results: Our algorithm achieved a determination coefficient of 40% including the variables age, gender, weight, height, self-declared race, amiodarone use, enzyme inducers use, VKORC1 genotypes and predicted phenotypes according to CYP2C9 polymorphisms. Conclusion: Data suggest that our developed algorithm is more accurate than the IWPC algorithm when the application is focused on patients from the Brazilian population. Population-specific derivation and/or calibration of warfarin dosing algorithms may lead to improved performance compared with general use dosing algorithms currently available.