Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Republic of Korea.
Department of Clinical Pharmacology and Therapeutics, Chungbuk National University College of Medicine and Hospital, Chungcheongbuk-do, Republic of Korea.
Br J Clin Pharmacol. 2022 Sep;88(9):4100-4110. doi: 10.1111/bcp.15348. Epub 2022 Apr 22.
DWP16001 is a novel sodium-glucose cotransporter-2 inhibitor under development for the treatment of type 2 diabetes mellitus. This study was conducted to evaluate the pharmacokinetics, pharmacodynamics and safety of DWP16001 after single and multiple doses in healthy subjects.
A randomized, double-blind, placebo- and active-controlled, single- and multiple-dose study was conducted. Twelve subjects in each dose group received a single dose (0.2, 0.5, 1.0, 2.0 or 5.0 mg) or multiple doses (0.1, 0.3, 0.5, 1.0 or 2.0 mg once daily for 15 consecutive days) of DWP16001, dapagliflozin 10 mg or placebo at a ratio of 8:2:2. Serial blood and interval urine samples were collected for the pharmacokinetic and pharmacodynamic analyses. The safety and tolerability of DWP16001 were also assessed.
A dose-dependent increase in the urinary glucose excretion was observed after a single dose, and the steady state urinary glucose excretion was 50-60 g/d after multiple doses in the dose range of 0.3-2.0 mg. DWP16001 was rapidly absorbed with the time to peak plasma concentration of 1.0-3.0 hours, and it exhibited a mean elimination half-life of 13-29 hours. The systemic exposure to DWP16001 increased proportionally with multiple dose administrations in the range of 0.1-2.0 mg. DWP16001 was well tolerated in all dose groups.
DWP16001 induced glucosuria in a dose-dependent manner, and systemic exposure was observed after multiple doses. DWP16001 was well tolerated in single oral doses of up to 5.0 mg and in multiple oral doses of up to 2.0 mg.
DWP16001 是一种新型的钠-葡萄糖共转运蛋白 2 抑制剂，正在开发用于治疗 2 型糖尿病。本研究旨在评估 DWP16001 在健康受试者中单次和多次给药后的药代动力学、药效学和安全性。
进行了一项随机、双盲、安慰剂和阳性对照、单剂量和多剂量研究。每个剂量组的 12 名受试者接受单次剂量（0.2、0.5、1.0、2.0 或 5.0mg）或多次剂量（0.1、0.3、0.5、1.0 或 2.0mg，每日一次，连续 15 天）的 DWP16001、达格列净 10mg 或安慰剂，比例为 8:2:2。进行了药代动力学和药效学分析。还评估了 DWP16001 的安全性和耐受性。
单次给药后观察到尿糖排泄呈剂量依赖性增加，多次给药后 0.3-2.0mg 剂量范围内的稳态尿糖排泄量为 50-60g/d。DWP16001 吸收迅速，达峰时间为 1.0-3.0 小时，平均消除半衰期为 13-29 小时。在 0.1-2.0mg 范围内，多次给药后 DWP16001 的系统暴露呈比例增加。在所有剂量组中，DWP16001 的耐受性良好。
DWP16001 呈剂量依赖性诱导尿糖排泄，多次给药后可观察到系统暴露。单次口服剂量高达 5.0mg 和多次口服剂量高达 2.0mg 时，DWP16001 耐受性良好。
