Abstract
Purpose :
The objective of this study was to characterize the plasma pharmacokinetics (PK) and safety profile of brimonidine following a single dose and 5-day QID dosing of brimonidine tartrate ophthalmic solution 0.025% in healthy adult subjects.
Methods :
This was an open-label, single-center study. One drop of brimonidine 0.025% was administered bilaterally in eligible subjects (≥18 years), with plasma collections post-instillation at 0.25, 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 18, and 24 hours. Identically timed blood draws were performed following QID dosing for 5 days. Brimonidine plasma concentrations were determined by liquid chromatography-tandem mass spectrometry. Safety parameters included adverse events (AEs), comprehensive ophthalmic exams, physical exams, vital signs, and clinical laboratory evaluations.
Results :
A total of 14 subjects (ages 19-46; mean 27.3) were enrolled; the majority of subjects were female (64.3%). Plasma concentrations of brimonidine were below the lower limit of quantitation (LLOQ=0.025 ng/mL) at all time points in 13/14 subjects. Only 1 subject had a detectable level (0.0253 ng/mL) at 1 time point (1 hour after a single dose). Seven subjects reported 8 non-serious AEs: 2 ocular AEs of transient mild hyperemia considered related to treatment in 2 subjects, and 6 non-ocular AEs of mild/moderate severity in 5 subjects, only one of which (headache) was deemed related to treatment. One subject was discontinued due to a non-ocular AE unrelated to study medication (bilateral antecubital bruising); all other safety exam findings were within normal range.
Conclusions :
These data indicate that topical ophthalmic administration of brimonidine 0.025% results in negligible systemic exposure during and after 5 days of bilateral QID dosing. Consistent with previous studies, there were no safety concerns identified suggesting that brimonidine tartrate ophthalmic solution 0.025% is well-tolerated.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.