药学学报, 2014, 49(12): 1674-1683
引用本文:
孙谊, 李良, 周田彦, 卢炜. 基于模型的荟萃分析比较非布索坦与别嘌醇在痛风患者中的血尿酸下降应答率的影响[J]. 药学学报, 2014, 49(12): 1674-1683.
SUN Yi, LI Liang, ZHOU Tian-yan, LU Wei. A model-based meta-analysis to compare urate-lowering response rate of febuxostat and allopurinol in gout patient[J]. Acta Pharmaceutica Sinica, 2014, 49(12): 1674-1683.

基于模型的荟萃分析比较非布索坦与别嘌醇在痛风患者中的血尿酸下降应答率的影响
孙谊, 李良, 周田彦, 卢炜
北京大学医学部药学院, 北京 100191
摘要:
采用基于模型的荟萃分析方法, 以患者血尿酸降至6 mg·dL-1以下的应答率作为临床终点, 对别嘌醇和非布索坦两种药物的药效进行比较.共计22项临床研究、43个剂量组、6 365名痛风患者被纳入本项研究.通过模型的建立, 分别探讨了别嘌醇和非布索坦的应答率随时间、剂量的变化规律, 以及血尿酸水平、别嘌醇非应答者对应答率的影响.结果表明, 使用别嘌醇治疗的平均最大应答率为50.8%.非布索坦药效良好, 给药后药效迅速达稳, 模型拟合得到非布索坦的ED50值为34.3 mg.患者基础血尿酸水平与别嘌醇应答率呈负相关, 而非布索坦的ED50随患者基础血尿酸水平的增加而增大.别嘌醇单独用药治疗效果不足患者, 其平均最大应答率约为别嘌醇应答者的1/2.
关键词:    痛风      血尿酸      应答率      别嘌醇      非布索坦     
A model-based meta-analysis to compare urate-lowering response rate of febuxostat and allopurinol in gout patient
SUN Yi, LI Liang, ZHOU Tian-yan, LU Wei
School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
Abstract:
This study aims to compare the urate-lowering response rate of febuxostat and allopurinol in gout patient using a model-based meta-analysis. The literature search identified 22 clinical trials of gout with a total of 43 unique treatment arms that met our inclusion criteria, and a total of 6 365 gout patients were included in the study. The response rates of allopuriol and febuxostat were characterized by Tmax model and Emax model respectively, and the effect of baseline serum uric acid (sUA) and patient type on the drug effect was tested. The results showed that allopurinol can reach an average maximum response rate of 50.8% while febuxostat can reach a 100% response rate within a very short time, and the ED50 was 34.3 mg. Covariate analysis revealed that baseline sUA has a negative effect on response rate of allopurinol, and a positive effect on the predicted ED50 of febuxostat. For patients who had shown inadequate response to prior allopurinol treatment, the average response rate was about half that of the allopurinol responder patients.
Key words:    gout    serum uric acid    response rate    allopurinol    febuxostat   
收稿日期: 2014-05-15
通讯作者: 卢炜
Email: luwei_pk@bjmu.edu.cn
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