摘要
目的分析华法林遗传学剂量预测模型(简称遗传学模型)预测剂量与实际治疗剂量不符的原因。方法通过参与2例服用华法林患者的抗凝治疗过程,分析华法林遗传学模型预测剂量与治疗剂量存在差异的原因,参与华法林的剂量调整,并对患者进行药学监护。结果 2例患者华法林敏感性基因检测结果分别为细胞色素P450 2C9(CYP2C9)*1/*3、维生素K环氧化物还原酶复合体1(VKORC1)-1639AA和CYP2C9*1/*1、VKORC1-1639 AA,最终的华法林治疗剂量与3种遗传学模型预测剂量不符,认为可能是由于其他影响华法林抗凝疗效的因素(如生理特性、其他基因位点多态性以及不良嗜好等)中的一个或多个因素的协同作用导致的。结论华法林存在显著个体差异,临床药师应综合考虑影响华法林疗效的因素,以临床抗凝疗效及国际标准化比值为标准,为患者提供个体化治疗方案,提高抗凝治疗的有效性和安全性。
Objective To analyze the possible causes for the inconsist- ency between the predicted results of the three genetic dose prediction models ( hereinafter referred to as: genetic models) and the actual thera- peutic doses of warfarin. Methods Through clinical pharmacists’inter- vention of two warfarin anticoagulated patients,the differences between genetic - based predicted doses and the actual therapeutic doses in these patients were analyzed,and the doses of warfarin were adjusted. Results Gene detection showed that the two patients were with the genotype of cytochrome P450 2C9 ( CYP2C9)* 1/* 3,vitamin K epoxide reductase complex 1 ( VKORC1)- 1639AA and CYP2C9* 1/* 1,VKORC1 - 1639 AA,respectively. And the actual warfarin therapeutic doses were not coincide with the predicted results of the three genetic models. Syner- gy of one or more affecting factors of warfarin anticoagulant efficacy ( such as physiological characteristics,other gene polymorphisms,and life style) were considered to be the potential leading causes. Conclusion There are significant individual differences in warfarin therapy. Clinical pharmacists should consider all the affecting factors and provide indivi- dualized anticoagulant therapy for patients based on clinical anticoagulant efficacy and international normalized ratio,to improve the effectiveness and safety of anticoagulant therapy.
作者
唐筱婉
都丽萍
梅丹
张波
王振苗
TANG Xiao-wan;DU Li-ping;MEI Dan;ZHANG Bo;WANG Zhen-miao(Department of Pharmacy,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences,Beijing 100730, China;Department of Pharmacy,The Second Affiliated Hospital of Hebei North University,Zhangjiakou 075100,Hebei Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2019年第15期1666-1668,共3页
The Chinese Journal of Clinical Pharmacology
基金
国家自然科学基金资助项目(81601033)
中国医学科学院医学与健康科技创新工程资助项目(2017-I2M1-011)
首都卫生发展科研专项资助项目(首发2018-3-4017)
关键词
华法林
遗传学剂量预测模型
个体差异
抗凝
临床药师
warfarin
genetic dose prediction models
individual variation
anticoagulant
clinical pharmacist
