P-One Clinic, Keikokai Medical Corporation, 8-1 Yokamachi, Hachioji, Tokyo, 192-0071, Japan.
Clinical Research Department, Mochida Pharmaceutical Co., Ltd., 1-22 Yotsuya, Shinjuku-ku, Tokyo, 160-0004, Japan.
Clin Exp Nephrol. 2020 Mar;24(Suppl 1):36-43. doi: 10.1007/s10157-020-01855-2. Epub 2020 Feb 19.
Dotinurad is a novel, selective urate reabsorption inhibitor, which reduces serum uric acid levels by inhibiting the urate transporter 1. The results of nonclinical studies indicated the possibility that the concomitant use of the non-steroidal anti-inflammatory drug oxaprozin affects the pharmacokinetics of dotinurad. We evaluated drug-drug interactions with respect to the pharmacokinetics and safety of dotinurad when co-administered with oxaprozin.
This was an open-label, two-period, add-on study in healthy adult males. For a single dose of 4 mg of dotinurad with and without oxaprozin, we compared its pharmacokinetic parameters and evaluated safety.
This study enrolled 12 subjects, 11 of whom completed the study. The geometric mean ratio (90% confidence interval [CI]) of the urinary excretion rate of glucuronate conjugates of dotinurad after co-administration with oxaprozin compared to administration of dotinurad alone was 0.657 (0.624-0.692), while the geometric mean ratios (90% CIs) of the maximum plasma concentration and area under the plasma concentration-time curve from time zero to infinity (AUC) were 0.982 (0.945-1.021) and 1.165 (1.114-1.219), respectively. During the study, two adverse events occurred after administration of dotinurad alone and one occurred after administration of oxaprozin alone.
In comparison with administration of dotinurad alone, co-administration with oxaprozin was associated with a 34.3% decrease in the urinary excretion rate of the glucuronate conjugates of dotinurad, and a 16.5% increase in AUC of dotinurad. However, no clinically meaningful drug-drug interactions were observed. Administration of dotinurad alone was similar safety to co-administration with oxaprozin.
ClinicalTrials.gov Identifier: NCT03350386.
多尼努拉德是一种新型、选择性尿酸重吸收抑制剂，通过抑制尿酸转运蛋白 1 降低血清尿酸水平。非临床研究结果表明，同时使用非甾体抗炎药奥沙普嗪可能会影响多尼努拉德的药代动力学。我们评估了多尼努拉德与奥沙普嗪同时使用时对其药代动力学和安全性的药物相互作用。
这是一项在健康成年男性中进行的开放性、两周期、附加研究。对于多尼努拉德单剂量 4mg 与奥沙普嗪合用与单用相比，我们比较了其药代动力学参数并评估了安全性。
这项研究共纳入 12 名受试者，其中 11 名完成了研究。与单独使用多尼努拉德相比，合用奥沙普嗪后多尼努拉德葡萄糖醛酸缀合物的尿排泄率的几何均数比值（90%置信区间[CI]）为 0.657（0.624-0.692），而最大血浆浓度和从零时到无穷大的血浆浓度-时间曲线下面积（AUC）的几何均数比值（90%CI）分别为 0.982（0.945-1.021）和 1.165（1.114-1.219）。在研究期间，单独使用多尼努拉德后发生了 2 起不良事件，单独使用奥沙普嗪后发生了 1 起不良事件。
与单独使用多尼努拉德相比，合用奥沙普嗪与多尼努拉德葡萄糖醛酸缀合物的尿排泄率降低 34.3%，AUC 增加 16.5%。然而，未观察到有临床意义的药物相互作用。单独使用多尼努拉德的安全性与合用奥沙普嗪相似。
ClinicalTrials.gov 标识符：NCT03350386。
