Medical Affairs Department, Mochida Pharmaceutical Co., Ltd, Tokyo, Japan.
Medical Affairs Division, Medical Communication Department, Fuji Yakuhin Co., Ltd, Tokyo, Japan.
Clin Pharmacol Drug Dev. 2024 Jan;13(1):87-95. doi: 10.1002/cpdd.1317. Epub 2023 Aug 9.
Dotinurad has been approved in Japan as a selective urate reabsorption inhibitor for the treatment of gout and hyperuricemia. The relationship between uric acid crystallization and the use of uricosuric drugs is widely acknowledged; however, the relationship between changes in urinary uric acid concentration and urine pH or volume has not been sufficiently analyzed. Therefore, we investigated the changes in urinary uric acid concentration following dotinurad administration as well as the relationship between urine pH or volume and urinary uric acid concentration. This post hoc analysis used data from 2 clinical trials that included 12 and 26 patients with hyperuricemia who received dotinurad treatment (for 7 days on an inpatient basis and 14 weeks on an outpatient basis, respectively). The urinary uric acid concentration transiently increased in the early stages of dotinurad use and when its dose was increased, but decreased over time. No uric acid concentrations exceeded the soluble limit at any urine pH. An inverse correlation was observed between urine volume and urinary uric acid concentration. This study highlights the significance of adequately managing urinary uric acid concentrations by increasing urine volume and alkalinizing urine to prevent uric acid crystallization during dotinurad administration.
多尼鲁单抗在日本被批准用于治疗痛风和高尿酸血症，是一种选择性尿酸重吸收抑制剂。尿酸结晶与促尿酸排泄药物的使用之间的关系是广泛认可的；然而，尿液中尿酸浓度的变化与尿液 pH 值或体积之间的关系尚未得到充分分析。因此，我们研究了多尼鲁单抗给药后尿液中尿酸浓度的变化，以及尿液 pH 值或体积与尿液中尿酸浓度之间的关系。本事后分析使用了两项临床试验的数据，这些试验共纳入了 12 名和 26 名高尿酸血症患者，他们接受了多尼鲁单抗治疗（分别在住院基础上进行 7 天和在门诊基础上进行 14 周）。在多尼鲁单抗使用的早期和剂量增加时，尿液中尿酸浓度短暂升高，但随着时间的推移逐渐降低。在任何尿液 pH 值下，尿酸浓度都没有超过可溶性极限。尿液体积与尿液中尿酸浓度呈负相关。本研究强调了在多尼鲁单抗给药期间，通过增加尿液量和碱化尿液来充分管理尿液中尿酸浓度的重要性，以防止尿酸结晶。
