Gupta Ajay, Sharma Pramod Kumar, Misra Arup Kumar, Singh Surjit
Department of Pharmacology, All India Institute of Medical Sciences, Jodhpur, Rajasthan, India.
J Pharmacol Pharmacother. 2016 Oct-Dec;7(4):155-158. doi: 10.4103/0976-500X.195897.
Gout is a metabolic disorder that usually presents as recurrent episodes of acute arthritis due to deposition of crystals in joints and cartilages. Despite the availability of several drugs for gout, its management is still less than adequate. There is always a search for newer, safer, and more potent urate-lowering therapies for treating patients inadequately controlled with available drugs. Lesinurad in combination with a xanthine oxidase inhibitor provides an effective mode of therapy in the management of hyperuricemia associated with gout. Lesinurad is a selective uric acid transporter 1 (URAT1) inhibitor. URAT1 is responsible for the majority of uric acid absorption from kidneys to the circulation. Lesinurad was granted marketing approval based on three randomized, double-blind, placebo-controlled; phase III clinical trials. It is devoid of interaction with organic anion transporters (OATs) such as OAT1 and 3, responsible for drug-drug interactions, an undesirable property associated with probenecid. On-going research is more focused on reducing inflammation consequent to deposition of crystals rather than production and excretion of urate. Various targets are being explored, and interleukin-1 beta inhibition seems to be one of the most promising approaches.
痛风是一种代谢紊乱疾病，通常表现为由于关节和软骨中晶体沉积导致的急性关节炎反复发作。尽管有几种治疗痛风的药物，但对其管理仍不尽如人意。一直在寻找更新、更安全、更有效的降尿酸疗法来治疗那些使用现有药物控制不佳的患者。雷西纳德与黄嘌呤氧化酶抑制剂联合使用，为治疗与痛风相关的高尿酸血症提供了一种有效的治疗模式。雷西纳德是一种选择性尿酸转运蛋白1（URAT1）抑制剂。URAT1负责肾脏向循环系统中大部分尿酸的重吸收。雷西纳德基于三项随机、双盲、安慰剂对照的III期临床试验获得了上市批准。它与负责药物相互作用的有机阴离子转运体（OATs）如OAT1和OAT3没有相互作用，而丙磺舒具有这种不良特性。正在进行的研究更多地集中在减少晶体沉积后的炎症反应，而不是尿酸的产生和排泄。正在探索各种靶点，抑制白细胞介素-1β似乎是最有前景的方法之一。
