Plasma Pharmacokinetic Parameters of Dexamethasone Following Administration of a Dexamethasone Intracanalicular Insert in Healthy Adults.

ABSTRACT

PURPOSE: Intracanalicular dexamethasone insert is a resorbable sustained-release polyethylene glycol-based hydrogel insert delivering a 0.4 mg tapered dose of dexamethasone for up to 30 days to the ocular surface. It is FDA-approved for treating inflammation and pain after ocular surgery. It has also been studied for ocular surface diseases such as allergic conjunctivitis. This study assessed the plasma pharmacokinetic (PK) parameters of dexamethasone following intracanalicular insertion. PATIENTS AND METHODS: Study subjects (N=16) were healthy adults. A dexamethasone insert was unilaterally placed into the canaliculus, and blood samples were obtained for analysis 1 hour prior to insertion and 1, 2, 4, 8, 16, 24 hours and 4, 8, 15, 22 and 29 days after insertion. Safety analyses included slit lamp and dilated fundus examinations, best corrected visual acuity, intraocular pressure (IOP) and adverse events (AEs). RESULTS: Plasma results were below the lower limit of quantitation (LLOQ) at all time points in five subjects (31.3%). Among subjects with quantifiable plasma concentrations, Cmax was <1 ng/mL (range, 0.05 to 0.81 ng/mL), AUC0-last ranged from 0.13 to 7.18 h∙ng/mL, and Tmax ranged from 4.0 to 163.0 hours. Mean (SD) IOP increased from 16.3 (1.4) mmHg at baseline to 19.3 (3.2) at Day 22 but returned to baseline after treatment. No changes occurred in dilated fundus, punctum, or visual acuity examinations. CONCLUSION: The dexamethasone 0.4 mg insert results in minimal systemic exposure following intracanalicular administration.