RESUMEN
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 (â¼6.3 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.
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PURPOSE: This study compares outcomes of therapy with OC-01 (varenicline solution) for dry eye disease in study eyes and nonstudy fellow eyes of participants in 2 pivotal clinical trials. METHODS: All 891 patients randomized to receive OC-01 (varenicline solution) 0.03 mg, OC-01 (varenicline solution) 0.06 mg, or vehicle control (VC) in each nostril twice daily for 28 days in the Phase IIb ONSET-1 (Evaluation of the Efficacy of OC-01 Nasal Spray on Signs and Symptoms of Dry Eye Disease) and Phase III ONSET-2 trials were included in this post hoc analysis. One eye was designated as the study eye. The mean change from baseline in anesthetized Schirmer test score (STS) and the percentage of eyes achieving a ≥10-mm STS improvement were compared between treatments in study and fellow eyes overall and by baseline Eye Dryness Score. FINDINGS: In the study eyes, the mean STS improvement from baseline to day 28 was 10.4 mm, 10.5 mm, and 4.9 mm in the 0.03 mg, 0.06 mg, and VC groups, respectively; comparable values in nonstudy fellow eyes were 8.7 mm, 8.8 mm, and 2.7 mm, respectively. The percentages of study eyes achieving a ≥10-mm STS improvement were 48.1%, 48.4%, and 25.9%, respectively, whereas the comparable values in nonstudy eyes were 42.9%, 43.9%, and 19.7%, respectively. No significant treatment-subgroup interactions were observed in study or fellow eye STS outcomes by baseline Eye Dryness Scores <40 and ≥40 (p > 0.05 for all). IMPLICATIONS: OC-01 (varenicline solution) nasal spray had significant tear film production improvements compared with VC in both study and fellow eyes. These findings suggest efficacy across a broad spectrum of presenting disease severity.
