Abstract：
Purpose: To evaluate the ocular and systemic pharmacokinetics of lotilaner ophthalmic solution, 0.25%, following bilateral topical ocular administration of single and repeated doses in rabbits. Methods: Dutch-belted rabbits (n = 34) were administered lotilaner ophthalmic solution, 0.25%, eye drops, either in a single bilateral dose (Group 1) or twice a day bilaterally for 7 days and once on Day 8 (Group 2). The pharmacokinetics and tissue distribution levels of lotilaner were assessed following the single dose in Group 1 and the last dose in Group 2. The drug levels were examined in various ocular tissues and whole blood. The maximal concentration of the drug (Cmax), time to maximal concentration, the terminal phase elimination half-life, the area under the concentration-time curve (AUC), and total clearance of the drug were determined. Results: In the eyelid margins, lotilaner exhibited the highest observed concentrations at 0.25 hour (h), presenting a mean Cmax of 14,600 ng/mL in Group 1 and 20,100 ng/mL in Group 2. The highest AUC was in the eyelid margin at 242,000 h×ng/mL in Group 1 and 535,000 h×ng/mL in Group 2. In the eyelid margin, the observed clearance rate (0.634 mL/h in single dose, 0.288 mL/h in repeat dose) was the slowest among all ocular tissues in both groups, with the longest half-life of 152 h (∼6.3 days) observed in the repeat dose group. Conclusions: Lotilaner ophthalmic solution, 0.25%, demonstrated rapid ocular tissue absorption into the eyelid margin tissue with a long half-life of almost a week. No adverse effects were observed following topical ocular administration in Dutch-belted rabbits.
摘要：
目的：评价洛替兰尔眼用溶液的眼部和全身药代动力学，0.25%,在兔中单次和重复剂量的双侧局部眼部给药。方法：荷兰束带兔（n=34）服用lotilaner眼用溶液，0.25%,眼药水,以单个双侧剂量(组1)或每天两次,持续7天,并且在第8天一次(组2)。在组1中的单剂量和组2中的最后剂量后评估lotilaner的药代动力学和组织分布水平。在各种眼组织和全血中检查药物水平。药物的最大浓度（Cmax），达到最大浓度的时间，终末期消除半衰期，浓度-时间曲线下面积（AUC），并确定药物的总清除率。结果：在眼睑边缘，lotilaner在0.25小时（h）时表现出最高的观察浓度，第1组的平均Cmax为14,600ng/mL，第2组的平均Cmax为20,100ng/mL。AUC最高在眼睑边缘，在第1组中为242,000h×ng/mL，在第2组中为535,000h×ng/mL。在眼睑边缘，观察到的清除率（单剂量为0.634mL/h，重复剂量0.288mL/h）在两组的所有眼组织中最慢，在重复剂量组中观察到的最长半衰期为152小时(~6.3天)。结论：Lotilaner眼用溶液，0.25%,表现出快速的眼部组织吸收到眼睑边缘组织中，具有近一周的长半衰期。在荷兰束带兔中局部眼部给药后未观察到不良反应。
