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新型黄嘌呤氧化酶抑制剂。

Novel uricosurics.

机构信息

Université Paris 7, UFR médicale, Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisière, Service de Rhumatologie.

INSERM UMR-1132, Hôpital Lariboisière, and Université Paris Diderot, Sorbonne Paris Cité, Paris, France.

出版信息

Rheumatology (Oxford). 2018 Jan 1;57(suppl_1):i42-i46. doi: 10.1093/rheumatology/kex433.

DOI:10.1093/rheumatology/kex433

PMID:29272511

Abstract

OBJECTIVE

According to recent guidelines, the mainstay of urate-lowering therapies remains xanthine oxidase inhibition. However, some patients with gout show failure to achieve the predefined target of 5-6 mg/dl with xanthine oxidase inhibitors alone, so alternative drugs are needed. The aim of this study was to review studies of novel drugs targeting uric acid transporter 1 (URAT1) and/or other urate transporters for the management of gout.

METHODS

MeSH terms were used to identify phase 2/3 trials assessing the efficacy of novel uricosurics. A narrative review of novel drugs targeting URAT1 and/or other urate transporters for the management of gout is provided.

RESULTS

Lesinurad is a recently approved uricosuric that inhibits URAT1 and the organic ion transporter organic anion transporter 4 (OAT4). Phase 3 trials showed that lesinurad, combined with allopurinol or febuxostat, is a potent urate-lowering therapeutic with an acceptable safety profile. Arhalofenate, another emerging uricosuric, also interacts with URAT1 and organic anion transporter 4. Phase 2 trials suggested that it can both lower serum UA levels and reduce the risk of flares.

CONCLUSIONS

New drugs inhibiting URAT1 should cover the unmet need for patients with failure to respond or with contraindications to xanthine oxidase inhibitors.

摘要

目的

根据最近的指南，黄嘌呤氧化酶抑制剂仍然是降低尿酸治疗的主要方法。然而，一些痛风患者单独使用黄嘌呤氧化酶抑制剂无法达到预设的 5-6mg/dl 目标，因此需要替代药物。本研究旨在综述靶向尿酸转运蛋白 1（URAT1）和/或其他尿酸转运蛋白的新型药物治疗痛风的研究。

方法

使用 MeSH 术语来确定评估新型尿酸排泄剂疗效的 2/3 期试验。本文提供了一种针对痛风管理的靶向 URAT1 和/或其他尿酸转运蛋白的新型药物的叙述性综述。

结果

Lesinurad 是一种最近批准的尿酸排泄剂，可抑制 URAT1 和有机阴离子转运蛋白有机阴离子转运蛋白 4（OAT4）。3 期试验表明，lesinurad 与别嘌醇或非布司他联合使用，是一种有效的降尿酸治疗药物，具有可接受的安全性。另一种新兴的尿酸排泄剂 Arhalofenate 也与 URAT1 和有机阴离子转运蛋白 4 相互作用。2 期试验表明，它既能降低血清 UA 水平，又能降低发作风险。