Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul, Korea.
Department of Ophthalmology, Seoul National University College of Medicine and Bundang Hospital, Gyeonggi-do, Korea.
Clin Transl Sci. 2022 May;15(5):1123-1130. doi: 10.1111/cts.13226. Epub 2022 Feb 8.
For the long-term efficacy of dry eye disease treatment, relieving underlying inflammation is necessary. Imatinib mesylate is a novel ophthalmic formulation of imatinib mesylate, which is expected to alleviate inflammation by inhibiting the discoidin domain receptor 1 activity. This study aims to evaluate the safety and pharmacokinetics of imatinib mesylate in healthy subjects. A randomized, double-blind, placebo-controlled study was conducted. In a single ascending dose, 16 subjects received a single eye drop of imatinib mesylate 0.1%, 0.3%, or matching placebo. In the multiple ascending dose (MAD), subjects received multiple eye drops of imatinib mesylate 0.1%, 0.3%, or matching placebo once daily for 7 days. Safety and tolerability were assessed by ophthalmic examination, including the visual analog scale (VAS) to monitor the burning sensation in the eyes. A total of four treatment-emergent adverse events (TEAEs) occurred during the study. All TEAEs were mildly severe with no serious cases. VAS results in the 0.1% MAD group exhibited highest score of two points, whereas it was less than one point in others. Insignificant difference between the imatinib mesylate and placebo groups in the VAS results was seen. After a single dose administration of imatinib mesylate 0.1%, all plasma concentrations were below the lower limit of quantification. The peak plasma concentrations of imatinib were less than 0.54 µg/L in all groups. In conclusion, a single and multiple topical ophthalmic administration of imatinib mesylate was well-tolerated in healthy subjects. Because there was minimal systemic exposure to imatinib, the adverse effect in the body seems to be insignificant.
对于干眼症治疗的长期疗效，缓解潜在的炎症是必要的。甲磺酸伊马替尼是甲磺酸伊马替尼的一种新型眼科制剂，有望通过抑制盘状结构域受体 1 的活性来减轻炎症。本研究旨在评估甲磺酸伊马替尼在健康受试者中的安全性和药代动力学。这是一项随机、双盲、安慰剂对照的研究。在单次递增剂量中，16 名受试者接受了单眼滴注甲磺酸伊马替尼 0.1%、0.3%或匹配的安慰剂。在多次递增剂量（MAD）中，受试者每天接受单眼滴注甲磺酸伊马替尼 0.1%、0.3%或匹配的安慰剂一次，持续 7 天。通过眼科检查评估安全性和耐受性，包括视觉模拟量表（VAS）来监测眼睛的烧灼感。研究期间共发生了四起治疗后出现的不良事件（TEAE）。所有的 TEAEs 均为轻度严重，无严重病例。0.1%MAD 组的 VAS 结果最高得分为 2 分，而其他组的得分则低于 1 分。在 VAS 结果方面，甲磺酸伊马替尼组与安慰剂组之间没有显著差异。单次给予甲磺酸伊马替尼 0.1%后，所有血浆浓度均低于定量下限。所有组的甲磺酸伊马替尼的血浆峰浓度均低于 0.54μg/L。总之，健康受试者中单眼和双眼局部应用甲磺酸伊马替尼均耐受良好。由于系统暴露于甲磺酸伊马替尼的量极小，因此体内的不良反应似乎并不明显。
