Faculty of Functional Food and Wine, Shenyang Pharmaceutical University, Shenyang, China.
Expert Opin Drug Metab Toxicol. 2023 Dec;19(12):895-909. doi: 10.1080/17425255.2023.2287477. Epub 2024 Jan 12.
Hyperuricemia is a common metabolic disease, which is a risk factor for gouty arthritis and ureteral stones and may also lead to cardiovascular and chronic kidney disease (CDK). Therefore, hyperuricemia should be treated early. Xanthine oxidase inhibitors (XOIs) and uricosuric agents (UAs), which target uric acid, are two types of medications that are used to treat gout and hyperuricemia. XOIs stop the body from producing excessive uric acid, while UAs eliminate it rapidly via the kidneys. Urate transporter 1 (URAT1) belongs to the organic anion transporter family (OAT) and is specifically localized to the apical membrane of the epithelial cells of proximal tubules. Unlike other organic anion transporter family members, URAT1 identifies and transports organic anions that are primarily responsible for urate transport.
This article reviews the pharmacokinetics and pharmacodynamics of the existing URAT1 inhibitors to serve as a reference for subsequent drug studies.
The URAT1 inhibitors that are currently used as clinical drugs mainly include dotinurad, benzbromarone, and probenecid. Results indicate that RDEA3170 may be the most promising inhibitor, in addition to SHR4640, URC-102, and MBX-102, which are in the early stages of development.
高尿酸血症是一种常见的代谢性疾病，是痛风性关节炎和输尿管结石的危险因素，也可能导致心血管疾病和慢性肾脏病（CKD）。因此，高尿酸血症应及早治疗。黄嘌呤氧化酶抑制剂（XOIs）和尿酸排泄剂（UAs）是两种用于治疗痛风和高尿酸血症的药物，它们针对尿酸。XOIs 阻止身体产生过多的尿酸，而 UAs 通过肾脏迅速将其排出。尿酸转运蛋白 1（URAT1）属于有机阴离子转运体家族（OAT），特异性定位于近端肾小管上皮细胞的顶膜。与其他有机阴离子转运体家族成员不同，URAT1 识别并转运主要负责尿酸转运的有机阴离子。
本文综述了现有 URAT1 抑制剂的药代动力学和药效学，为后续药物研究提供参考。
目前用作临床药物的 URAT1 抑制剂主要包括多尼培拉德、苯溴马隆和丙磺舒。结果表明，除了处于早期开发阶段的 SHR4640、URC-102 和 MBX-102 之外，RDEA3170 可能是最有前途的抑制剂。
