Pharmacokinetics and safety of olopatadine hydrochloride 0.77% in healthy subjects with asymptomatic eyes: data from 2 independent clinical studies

摘要

Purpose: To assess the pharmacokinetics and safety of hydrochloride ophthalmic solution 0.77% olopatadine from 2 independent (Phase I and Phase III, respectively) clinical studies in healthy subjects. Materials and methods: The Phase I, multicenter, randomized (2:1), vehicle-controlled study was conducted in subjects ≥18?years old (N=36) to assess the systemic pharmacokinetics of olopatadine 0.77% following single- and multiple-dose exposures. The Phase III, multicenter, randomized (2:1), vehicle-controlled study was conducted in subjects ≥2?years old (N=499) to evaluate long-term ocular safety of olopatadine 0.77%. Subjects received olopatadine 0.77% or vehicle once daily bilaterally for 7?days in the pharmacokinetic study and 6?weeks in the safety study. Results: In the pharmacokinetic study, olopatadine 0.77% was absorbed slowly and reached a peak plasma concentration (C_max) of 1.65?ng/mL following single-dose and 1.45?ng/mL following multiple-dose exposures in 2?hours (time to reach maximum plasma concentration [T_max]). After reaching peak concentrations, olopatadine showed a similar mono-exponential decay following single and multiple doses with mean elimination half-life ranging from 2.90 to 3.40?hours. No accumulation in olopatadine exposure (C_max and area under the plasma concentration–time curve from 0 to 12?hours) was evident after multiple doses when compared to single dose. In the safety study, treatment-emergent adverse events were reported in 26.7% and 31.4% of subjects with olopatadine 0.77% and vehicle, respectively. Blurred vision was the most frequent ocular treatment-emergent adverse event in both treatment groups (olopatadine 0.77% vs vehicle, 4.8% vs 4.1%). No deaths or serious adverse events were reported during the study. Conclusion: Olopatadine 0.77% had minimal systemic exposure or accumulation in healthy subjects and was well tolerated in both adult and pediatric subjects.