华法林个体化剂量调整模型的建立和应用  

Establishment and Application of Warfarin Individual Dosage Adjustment Model

作　　者：杨晶晶[1] 于锋[1] 葛卫红[2] 阳丽梅 袁盛华[2] 朱怀军[2] 张延博[2] 

机构地区：[1]中国药科大学临床药学教研室,南京214001 [2]南京大学医学院附属鼓楼医院药剂科,南京210008 [3]福建省省立医院药剂科,福州350001

出　　处：《药学与临床研究》2010年第3期269-273,共5页Pharmaceutical and Clinical Research

摘　　要：目的:通过观察机械瓣膜置换术患者基线信息及CYP2C9、VKORC1基因多态性与术后个体华法林维持剂量的关系,建立剂量调整的模型。方法:按照设定标准纳入111例患者,以控制术后国际标准化比值(INR)在1.5～2.5为目标,调整合适的华法林维持剂量。采用PCR-RFLP(酶切)和测序技术对患者CYP2C9*3、VKORC1-1173、VKORC1-1639进行基因多态性检测,结合患者基线信息,多元逐步回归分析拟合得华法林剂量模型,并进行验证。结果:患者基线信息中年龄、身高与华法林剂量相关;VKORC1-1639位点GA型患者所需华法林剂量显著高于AA型患者。拟合得到给药模型为D=-1.034+1.229XVKORC1-1639-0.022A+0.021H。30例患者验证表明模型剂量(2.8529±0.6601)mg比平均实际剂量(3.1507±1.2940)mg偏低,t检验P<0.05,具有显著性差异,剂量差异为(0.2978±0.6339)mg。结论:模型可以解释35.8%的华法林剂量差异,该公式计算出的华法林剂量可以提高华法林抗凝初始阶段给药的精确性,提高患者用药安全性。Objective：To explore relationship between warfarin maintain dose with patients＇ baseline information and the polymorphisms of CYP2C9 and VKORC1 after mechanical heart valve prostheses implantation and to establish a dose adjustment model in this population.Method：Based on the specified standard,111 patients were received and their International Normalized Ratios（INR） after operation were controlled between 1.5 and 2.5 with proper warfarin maintain doses.PCR-RFLP and sequencing technology were used to examine the genetypes of CYP2C9＊3,VKORC1-1173 and VKORC1-1639.Warfarin dose model was acquired by multiple stepwise regression analysis and furthermore verified.Result：Among the baselines of patients,their ages and heights were related to warfarin dose;VKORC1-1639 GA-type patents required higher warfarin doses than AA-type ones.By fitting,a medication model D=-1.034＋1.229XVKORC1-1639-0.022A＋0.021H was obtained.It was verified by 30 patents that the model dose（2.8529±0.6601）mg was lower than the actual average one equaling to 3.1507±1.2940mg.T-test P was lower than 0.05.There were distinctive dose differences equaling to（0.2978±0.6339） mg.Conclusion：The model can explain the warfarin dose difference by 35.8%.This equation can improve the accuracy and safety of drug administration in the preliminary warfarin anti-coagulation stage.

关 键 词：华法林 基因多态性 剂量需求 给药模型 

分 类 号：R969[医药卫生—药理学]