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, C_max was <1 ng/mL (range, 0.05 to 0.81 ng/mL), AUC_0-last ranged from 0.13 to 7.18 h∙ng/mL, and T_max 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

Acknowledgment

The authors acknowledge the editorial assistance of Dr. Carl S. Hornfeldt, Apothekon, Inc., during the preparation of this manuscript and David Evans, OD, Total Eye Care, Memphis, TN, Deepa Mulani, MS, and Jonathan H Talamo, MD, Ocular Therapeutix, Inc., and Robert Noecker, MD, Ophthalmic Consultants of Connecticut, Fairfield, CT for their early contributions to this study. This study was sponsored by Ocular Therapeutix, Inc., Bedford, MA. The abstract of this paper was presented at the 2017 ARVO Annual Meeting, Baltimore, MD; May 7–11, 2017 which appeared in Invest Ophthalmol Vis Sci. 2017;58. Available from: https://iovs.arvojournals.org/article.aspx?articleid=2638122.

Author Contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

Michael H Goldstein, Srilatha Vantipalli, Jamie Lynne Hart, Fabiana Q Silva, Charles Blizzard, and Arthur Driscoll are employees of and owned stocks for Ocular Therapeutix who was the sponsor for the study and who commercializes DEXTENZA. Mr Charles Blizzard has a patent issued: US20160331738A1 - Drug Delivery Through Hydrogels. Eugene B McLaurin is affiliated with Total Eye Care and is an investigator in a clinical trial sponsored by Ocular Therapeutix. The authors report no other conflicts of interest in this work.