R -群体药物动力学和S-warfarin:遗传和临床因素的影响。

文章的细节

引用
复制到剪贴板

巷,Al-Zubiedi年代,舱口E,马修斯,约根森,Deloukas P,戴利AK,公园BK,亚伦L, Ogungbenro K, Kamali F,休斯D, Pirmohamed M

R -群体药物动力学和S-warfarin:遗传和临床因素的影响。

Br中国新药杂志。2012年1月,73 (1):66 - 76。doi: 10.1111 / j.1365-2125.2011.04051.x。

PubMed ID
21692828 (在PubMed
]
文摘

背景:华法林是药物治疗指数窄和大型个人间变异性在日常计量的要求。病人开始华法林治疗出血的风险是由于过度抗凝用药过量所致。剂量需求的个人间的变化受到很多因素的影响,包括基因的多态性调停华法林药理学,co-medication,年龄、性别、体型和饮食。目的:开发群体药代动力学模型R -和S-warfarin协变量使用临床和遗传因素和识别影响个人间间隙的药代动力学参数和体积的变化分布在长期华法林治疗患者。方法:患者华法林治疗随访26周开始。等离子体在306名患者华法林对映体浓度测定S-warfarin R-warfarin在1 309例,8和26周。患者也为CYP2C9基因变体(CYP2C9 * 1 * 2 * 3),两个单核苷酸多态性(SNP)在CYP1A2,一个SNP在CYP2C19 CYP3A4和六个SNP。基药代动力学模型是使用NONMEM软件开发的华法林间隙和体积分布。影响的协变量模型扩展到包括主客体之间的变化。结果:体重、年龄、性别和CYP2C9基因型明显S-warfarin间隙的影响。 The S-warfarin clearance was estimated to be 0.144 l h(-)(1) (95% confidence interval 0.131, 0.157) in a 70 kg woman aged 69.8 years with the wild-type CYP2C9 genotype, and the volume of distribution was 16.6 l (95% confidence interval 13.5, 19.7). Bodyweight and age, along with the SNPs rs3814637 (in CYP2C19) and rs2242480 (in CYP3A4), significantly influenced R-warfarin clearance. The R-warfarin clearance was estimated to be 0.125 l h(-)(1) (95% confidence interval 0.115, 0.135) in a 70 kg individual aged 69.8 years with the wild-type CYP2C19 and CYP3A4 genotypes, and the volume of distribution was 10.9 l (95% confidence interval 8.63, 13.2). CONCLUSIONS: Our analysis, based on exposure rather than dose, provides quantitative estimates of the clinical and genetic factors impacting on the clearance of both the S- and R-enantiomers of warfarin, which can be used in developing improved dosing algorithms.

DrugBank数据引用了这篇文章

药物
药物酶
药物 酶 类 生物 药理作用 行动
(R)华法林 细胞色素P450 1 a2 蛋白质 人类
未知的
底物
 细节