Kim Myong-Jin, Huang Shiew-Mei, Meyer Urs A, Rahman Atiqur, Lesko Lawrence J
Office of Clinical Pharmacology, Center for Drug Evaluation and Research, Food and Drug Administration, Rm 3188, Bldg 51, 10903 New Hampshire Avenue, Silver Spring, MD 20993-0002, USA.
J Clin Pharmacol. 2009 Feb;49(2):138-46. doi: 10.1177/0091270008328098.
Warfarin is a challenging drug to accurately dose, both initially and for maintenance, because of its narrow therapeutic range, wide interpatient variability, and long list of factors that can influence dosing. Two million people in the United States are initiated on warfarin therapy annually, and this number is steadily increasing because of the increase in number of eligible patients. Recently, warfarin was reported to be the fourth leading cause of adverse events. The U.S. Food and Drug Administration recognizes that the adverse event rate of warfarin can be improved through better initial dosing, because many of the serious adverse events of warfarin occur soon after starting treatment. A substantial number of studies demonstrate that common variants of two genes, VKORC1 and CYP2C9, along with other nongenetic factors, correlate significantly with warfarin dosing. The genotypes of VKORC1 and CYP2C9 alone account for nearly 3 times more of the variability ( approximately 30%) in warfarin dosing than do age, weight, gender, and other clinical factors combined ( approximately 12%). Therefore, the purpose of this report is to review the current recommendations for warfarin therapy that involve genetic testing.
华法林是一种在初始剂量和维持剂量方面都难以精确给药的药物，这是因为其治疗窗狭窄、患者间差异大，以及有众多可影响剂量的因素。美国每年有200万人开始接受华法林治疗，并且由于符合条件的患者数量增加，这一数字正在稳步上升。最近，华法林被报道为不良事件的第四大主要原因。美国食品药品监督管理局认识到，通过更好的初始给药可以提高华法林的不良事件发生率，因为华法林的许多严重不良事件在开始治疗后不久就会发生。大量研究表明，两个基因VKORC1和CYP2C9的常见变异，以及其他非遗传因素，与华法林剂量显著相关。仅VKORC1和CYP2C9的基因型对华法林剂量变异性的影响（约30%）就几乎是年龄、体重、性别和其他临床因素综合影响（约12%）的3倍。因此，本报告的目的是综述目前涉及基因检测的华法林治疗建议。
