TKL Research Inc., Fair Lawn, New Jersey, USA.
Velocity Clinical Research, San Diego, California, USA.
Clin Pharmacol Drug Dev. 2022 Mar;11(3):397-405. doi: 10.1002/cpdd.1041. Epub 2021 Nov 16.
Tirbanibulin is a novel tubulin polymerization and Src kinase signaling inhibitor. This study was designed to fully characterize tirbanibulin pharmacokinetics (PK) when applied topically under maximal use conditions. This was an open-label, parallel-group PK safety study of tirbanibulin ointment 1% applied to 25 cm of the face or balding scalp in adults with actinic keratosis (AK). Eligible subjects self-applied tirbanibulin once-daily for 5 days. PK sampling occurred on days 1, 3 and 4 at 0 hour (before dosing), and on day 5 at prespecified time points up to 24 hours after application. Safety assessments included adverse events and local skin reactions were evaluated up to day 29. Eighteen subjects (face or scalp, n = 9 each) completed the study. Subjects were White (100%), of mean [range] age 66.4 [43-83] years, predominantly men (83.3%) with Fitzpatrick skin type I to III (94.4%); baseline AK lesion count, mean [range] 8.2 [6-14]. All subjects had quantifiable but low plasma concentrations of tirbanibulin. On day 5, overall mean (standard deviation) maximum concentration (C ) was 0.26 (0.23) ng/mL (or 0.60 nM), median time to maximum concentration was 6.91 hours, and mean (standard deviation) area under the plasma concentration-time curve from time 0 to 24 hours was 4.09 (3.15) ng ∙ h/mL. Four subjects experienced a total of 5 treatment-emergent adverse events that resolved. Mild to moderate erythema, flaking, or scaling in the treatment area peaked around day 8 before resolving or returning to baseline by day 29. In conclusion, under maximal use conditions, tirbanibulin ointment 1% for 5 days in the treatment of AK on the face or scalp was well tolerated and resulted in low systemic exposure with subnanomolar plasma concentrations.
替比嘧啶是一种新型的微管蛋白聚合和Src 激酶信号抑制剂。本研究旨在充分描述替比嘧啶在最大使用条件下经皮应用时的药代动力学（PK）特征。这是一项开放标签、平行组 PK 安全性研究，评估 1%替比嘧啶软膏应用于 25cm 的面部或脱发头皮，治疗成人光化性角化病（AK）。符合条件的受试者每天自我应用替比嘧啶一次，连续 5 天。PK 采样在第 1、3 和 4 天的 0 小时（给药前）进行，第 5 天在指定时间点进行，直到应用后 24 小时。安全性评估包括不良事件，局部皮肤反应评估至第 29 天。18 名受试者（面部或头皮，n = 9）完成了研究。受试者均为白人（100%），平均年龄为 66.4 [43-83] 岁，男性为主（83.3%），皮肤类型为 I 至 III 型（94.4%）；基线 AK 病变计数，平均[范围]为 8.2 [6-14]。所有受试者的替比嘧啶血浆浓度均可定量，但浓度较低。第 5 天，总体平均（标准差）最大浓度（C ）为 0.26（0.23）ng/mL（或 0.60 nM），中位达峰时间为 6.91 小时，0 至 24 小时的血浆浓度-时间曲线下面积为 4.09（3.15）ng·h/mL。4 名受试者共发生 5 例治疗后不良事件，均已解决。治疗区域的轻度至中度红斑、脱屑或鳞屑在第 8 天左右达到峰值，然后在第 29 天恢复或回到基线。总之，在最大使用条件下，替比嘧啶软膏 1%连续使用 5 天治疗面部或头皮 AK 的安全性良好，全身暴露程度低，血浆浓度接近纳摩尔水平。
