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

Autor: Jamie Lynne Metzinger, Arthur Driscoll, Michael H Goldstein, Eugene B McLaurin, Charles D Blizzard, Fabiana Q. Silva, Srilatha Vantipalli
Rok vydání: 2021
Předmět:
Zdroj: Clinical Ophthalmology (Auckland, N.Z.)
ISSN: 1177-5483
Popis: Charles Blizzard,1 Eugene B McLaurin,2 Arthur Driscoll,1 Fabiana Q Silva,1 Srilatha Vantipalli,1 Jamie Lynne Metzinger,1 Michael H Goldstein1 1Ocular Therapeutix, Inc., Bedford, MA, USA; 2Total Eye Care, Memphis, TN, USACorrespondence: Srilatha VantipalliOcular Therapeutix, Inc, 24 Crosby Drive, Bedford, MA, 01730, USAEmail SVantipalli@ocutx.comPurpose: 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.Keywords: intracanalicular dexamethasone, plasma pharmacokinetics, sustained-release insert, safety assessments
Databáze: OpenAIRE
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