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OALib Journal期刊
ISSN: 2333-9721
费用：99美元
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基于nonmem法的华法林群体药动学/药效学模型研究
, PP. 1280-1284
Keywords: 华法林,cyp2c9,vkorc1,群体药动学/药效学
Abstract:
本研究旨在建立中国人华法林群体药动学/药效学(ppk/pd)模型。研究中收集接受华法林治疗的73例患者190个血样,pcr-rflp法检测患者cyp2c9及vkorc1基因分型,rp-hplc-uv法测定华法林血药浓度。结合临床资料及263个国际标准化比值(inr)监测值,应用nonmem软件考察患者遗传、生理、病理因素及合并用药等对华法林清除率及抗凝指标的影响,建立了华法林ppk/pd最终模型:cl=θcl·(wt/60)θwt·θcyp·eηcl;ec50=θec50·θvkor·eηec50;v=θv;ke0=θke0;emax=θemax;e0=θe0·eηe0。其中体重、cyp2c9及vkorc1基因分型是影响华法林药动学/药效学参数的主要因素。经拟合优度诊断、bootstrap法、npde验证显示,模型稳定、有效,具有良好的拟合优度与预测能力。
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