The Pharmacodynamics, Pharmacokinetics, and Safety of Arhalofenate in Combination with Febuxostat When Treating Hyperuricemia Associated with Gout
The Pharmacodynamics, Pharmacokinetics, and Safety of Arhalofenate in Combination with Febuxostat When Treating Hyperuricemia Associated with Gout
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阿卤芬酯联合非布索坦治疗痛风相关高尿酸血症的药效学、药代动力学及安全性
DOI：
10.3899/jrheum.161062
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发表时间：
2017
期刊：
影响因子：
--
通讯作者：
P. Boudes
中科院分区：
文献类型：
--
作者：
A. Steinberg;B. Vince;Yun;Robert L. Martin;C. McWherter;P. Boudes
Objective.阿卤芬酸（ARH），在开发痛风，具有尿酸和抗耀斑活动。在痛风受试者中评估ARH加非布司他（FBX）的血清尿酸（SUA）降低、药物相互作用和安全性。方法.痛风志愿者开放II期试验（NCT 02252835）。队列1接受ARH 600 mg给药2周，随后连续1周联合给予FBX 80 mg，随后40 mg。单独继续服用FBX 40 mg 2周。队列2接受ARH 800 mg治疗2周，随后连续1周联合给予FBX 40 mg，随后80 mg。FBX 80 mg单独给药持续2周。评估SUA、其排泄分数（FEUA）和血浆氧嘌呤。在队列2中，测定了FBX和ARH单独给药和联合给药的药代动力学。结果队列1（n = 16）的基线平均SUA为9.4 mg/dl，队列2（n = 16）为9.2 mg/dl。ARH 800 mg + FBX 80 mg组SUA下降幅度最大（63%），所有受试者均达到SUA < 6 mg/dl，93% < 5 mg/dl。ARH酸+ FBX/ARH酸的曲线下面积（AUC）（0-t）为108%。FBX + ARH酸/FBX的AUC（0-t）为87%。正如预期的那样，FBX增加了氧化嘌呤，并且增加不受ARH联合给药的影响。基线FEUA较低（3.5%-4.6%），ARH使其增加至正常水平，但不过度分泌UA。ARH耐受性良好，似乎安全。结论ARH和FBX通过互补机制降低SUA。该组合提供了比每种药物单独使用更大的降低。该组合耐受性良好，似乎是安全的。试验注册：NCT 02252835。
Objective. Arhalofenate (ARH), in development for gout, has uricosuric and anti-flare activities. ARH plus febuxostat (FBX) were evaluated in subjects with gout for serum uric acid (SUA) lowering, drug interaction, and safety. Methods. Open phase II trial in gout volunteers (NCT02252835). Cohort 1 received ARH 600 mg for 2 weeks, followed by sequential 1-week co-administration of FBX 80 mg followed by 40 mg. FBX 40 mg was continued alone for 2 weeks. Cohort 2 received ARH 800 mg for 2 weeks, followed by sequential 1-week co-administration of FBX 40 mg followed by 80 mg. FBX 80 mg was continued alone for 2 weeks. SUA, its fractional excretion (FEUA), and plasma oxypurines were assessed. Pharmacokinetics of FBX and ARH were determined alone and in combination for cohort 2. Results. Baseline mean SUA was 9.4 mg/dl for cohort 1 (n = 16) and 9.2 mg/dl for cohort 2 (n = 16). The largest SUA decrease (63%) was observed with ARH 800 mg + FBX 80 mg, with all subjects reaching SUA < 6 mg/dl and 93% < 5 mg/dl. The area under the curve (AUC)(0-t) of ARH acid + FBX/ARH acid was 108%. The AUC(0-t) of FBX + ARH acid/FBX was 87%. As expected, FBX increased oxypurines and increases were unaffected by ARH co-administration. Baseline FEUA were low (3.5%–4.6%) and ARH increased them toward normal without overexcretion of UA. ARH was well tolerated and appeared safe. Conclusion. ARH and FBX lowered SUA by complementary mechanisms. The combination provided greater decreases than each drug alone. The combination was well tolerated and appeared safe. Trial registration: NCT02252835.
纵向研究中痛风复发发作管理不当的频率和预测因素。
DOI：
--
发表时间：
2006
期刊：
The Journal of rheumatology
影响因子：
--
作者：
Neogi,Tuhina;Hunter,DavidJ;Chaisson,ChristineE;Allensworth-Davies,Donald;Zhang,Yuqing
通讯作者：
Zhang,Yuqing
影响因子：
5.9
作者：
Keenan, Robert T.;O'Brien, William R.;Pillinger, Michael H.
通讯作者：
Pillinger, Michael H.