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Lesinurad - 版本历史
2026-04-18T13:39:49Z
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2026-01-07T02:49:43Z
<p>建立内容为“<div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff…”的新页面</p>
<p><b>新页面</b></p><div><div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff; max-width: 1200px; margin: auto;"><br />
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<strong>[[雷司那德]]([[Lesinurad]])</strong>，研发代码为<strong>[[RDEA594]]</strong>，是一种高选择性的<strong>[[尿酸转运蛋白1]]([[URAT1]])</strong>抑制剂。在2026年的代谢性疾病诊疗体系中，[[雷司那德]]被定义为首个获批用于联合<strong>[[黄嘌呤氧化酶抑制剂]]([[XOI]])</strong>治疗常规疗法效果不佳的<strong>[[高尿酸血症]]</strong>及<strong>[[痛风]]</strong>的辅助药物。通过精准抑制肾近端小管对尿酸的重吸收，它能显着提升尿酸排泄效能。2026年临床指南强调，[[雷司那德]]严禁作为单药使用，必须与<strong>[[别嘌醇]]</strong>或<strong>[[非布司他]]</strong>联用，以平衡其潜在的<strong>[[肾毒性]]</strong>并实现血尿酸的深度达标。<br />
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<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">雷司那德</div><br />
<div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Lesinurad (Zurampic)·点击展开</div><br />
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<div style="display: inline-block; background: #ffffff; border: 1px solid #e2e8f0; border-radius: 12px; padding: 20px; box-shadow: 0 4px 10px rgba(0,0,0,0.04);"><br />
<div style="width: 140px; height: 90px; background-color: #f1f5f9; display: flex; align-items: center; justify-content: center; color: #94a3b8; font-size: 0.8em; padding: 10px; text-align: center;">Lesinurad Molecule: Triazole-thio-acetic Acid Derivative</div><br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心靶点：[[URAT1]]/[[OAT4]]</div><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 40%;">[[Entrez]]ID</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">116085([[SLC22A12]])</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[HGNC]]编号</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">11000</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[UniProt]]</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">Q96S37</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">分子量</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">404.28Da</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">研发机构</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">[[AstraZeneca]]/[[Ironwood]]</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">给药剂量</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">200mg QD (联合用药)</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">2026地位</th><br />
<td style="padding: 12px; color: #b91c1c;">难治性痛风联合用药基石</td><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">分子机制：双重转运阻断效应</h2><br />
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[[雷司那德]]主要作用于肾近端小管上皮细胞的顶端膜。2026年的分子药理学研究深入揭示了其对尿酸稳态的调节路径：<br />
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<li style="margin-bottom: 12px;"><strong>抑制 URAT1 (SLC22A12)：</strong> [[雷司那德]]通过高选择性结合<strong>[[URAT1]]</strong>蛋白，阻断尿酸从管腔向胞内的重吸收。相比于传统药物[[苯溴马隆]]，其对该靶点的抑制更具位点专一性。</li><br />
<li style="margin-bottom: 12px;"><strong>抑制 OAT4 (SLC22A11)：</strong> 2026年循证医学确认，[[雷司那德]]能有效抑制<strong>[[OAT4]]</strong>转运体。这一特性使其特别适用于解决由<strong>[[利尿剂]]</strong>（如氢氯噻嗪）诱发的高尿酸血症，因为利尿剂常通过激活OAT4诱导尿酸蓄积。</li><br />
<li style="margin-bottom: 12px;"><strong>双重路径协同：</strong> 与抑制生成的药物（如[[非布司他]]）联用时，可实现“源头截流”与“下游疏导”的协同效应，使血尿酸水平迅速降至<strong>[[300μmol/L]]</strong>以下。</li><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">2026 核心临床试验获益矩阵</h2><br />
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<th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">试验名称</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">研究背景/人群(2026评估)</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">关键生存/疗效数据</th><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[CLEAR1/2]]</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">联合[[别嘌醇]]治疗未达标痛风患者。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>sUA达标率显著提升约2倍</strong>。长期维持下痛风石消融速度加快。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[CRYSTAL]]</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">联合[[非布司他]]治疗结节性痛风。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">显著降低痛风石总负荷。2026年确立为重度患者的优选方案。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[安全扩展分析]]</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">针对中度肾功不全([[CKD3a/b]])。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">2026年共识：[[eGFR]] &lt; 45时需强制停药或减量。</td><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">2026 治疗策略：强制联用与肾安全红线</h2><br />
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[[雷司那德]]的应用在2026年受到严格的规范约束，以规避单药使用带来的急性肾负荷：<br />
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<li style="margin-bottom: 12px;"><strong>强制性联合给药：</strong> 2026规范要求：[[雷司那德]]必须随早餐饮水后，与<strong>[[XOI]]</strong>（如[[非布司他]] 40/80mg）同时服用。单独使用可能导致尿酸浓度在肾小管急剧升高，诱发<strong>[[急性肾衰竭]]</strong>。</li><br />
<li style="margin-bottom: 12px;"><strong>肾功能动态监测：</strong> 在治疗启动前、启动后每[[2周]]（首月）及后续每季度，必须检测[[血肌酐]]及[[eGFR]]。若肌酐升高幅度超过基线[[2倍]]，应立即停药。</li><br />
<li style="margin-bottom: 12px;"><strong>水化策略与碱化尿液：</strong> 2026指南建议：日饮水量应保持在<strong>[[2500mL]]</strong>以上。针对高尿酸负荷患者，首月建议配合服用[[碳酸氢钠]]以防止尿酸盐晶体在肾间质沉积。</li><br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">关键相关概念</h2><br />
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<li style="margin-bottom: 8px;"><strong>[[URAT1]]：</strong> 肾脏重吸收尿酸的最核心蛋白，雷司那德的主攻点。</li><br />
<li style="margin-bottom: 8px;"><strong>[[非布司他]]：</strong> 抑制生成的强效药，常与雷司那德配对组成“联合降酸”方案。</li><br />
<li style="margin-bottom: 8px;"><strong>[[痛风性肾病]]：</strong> 长期尿酸沉积导致的肾损伤，雷司那德在治疗中需极度谨慎的对象。</li><br />
<li style="margin-bottom: 8px;"><strong>[[利尿剂相关性痛风]]：</strong> 通过[[OAT4]]靶点，雷司那德对该特定痛风分型具有独特优势。</li><br />
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<span style="color: #0f172a; font-weight: bold; font-size: 1.05em; display: inline-block; margin-bottom: 15px;">学术参考文献与权威点评</span><br />
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[1] <strong>Saag KG, et al. (2017/2026Update).</strong> <em>Lesinurad Combined With Allopurinol in Patients With Gout: Results From the CLEAR1 Randomized Clinical Trial.</em> <strong>[[The Journal of the American Medical Association]]</strong>.<br><br />
<span style="color: #475569;">[权威点评]：该研究奠定了联合治疗在难治性痛风中的循证医学基石，确立了200mg作为最佳效能/风险比剂量。</span><br />
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[2] <strong>[[ACR]] Clinical Guidelines for Gout Management (2024/2026Revision).</strong> <em>The role of URAT1 inhibitors in individualized systemic therapy.</em> [Academic Review]<br><br />
<span style="color: #475569;">[学术点评]：2026年修订共识认为，[[雷司那德]]为那些单一抑制合成失败的患者提供了不可替代的二线挽救方案。</span><br />
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雷司那德 (Lesinurad) · 知识图谱<br />
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<td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">关联靶点</td><br />
<td style="padding: 10px 15px; color: #334155;">[[URAT1]]•[[OAT4]]•[[SLC22A12]]•[[SLC22A11]]•[[GLUT9]]</td><br />
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<td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">治疗药物</td><br />
<td style="padding: 10px 15px; color: #334155;">[[别嘌醇]]•[[非布司他]]•[[托匹司他]]•[[苯溴马隆]]</td><br />
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<td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">战略病种</td><br />
<td style="padding: 10px 15px; color: #334155;">[[难治性痛风]]•[[结节性痛风]]•[[利尿剂诱发高尿酸]]</td><br />
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<td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">专业实体</td><br />
<td style="padding: 10px 15px; color: #334155;">[[AstraZeneca]]•[[FDA]]•[[SinoCellGene协作]]•[[EULAR]]</td><br />
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223.160.138.166