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

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, Bed...

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Autores principales:	Blizzard C, McLaurin EB, Driscoll A, Silva FQ, Vantipalli S, Metzinger JL, Goldstein MH
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2021
Materias:	intracanalicular dexamethasone plasma pharmacokinetics sustained-release insert safety assessments Ophthalmology RE1-994
Acceso en línea:	https://doaj.org/article/a3d1044738c540a98e4e2930dfaa6914
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spelling	oai:doaj.org-article:a3d1044738c540a98e4e2930dfaa69142021-12-02T15:55:50ZPlasma Pharmacokinetic Parameters of Dexamethasone Following Administration of a Dexamethasone Intracanalicular Insert in Healthy Adults1177-5483https://doaj.org/article/a3d1044738c540a98e4e2930dfaa69142021-05-01T00:00:00Zhttps://www.dovepress.com/plasma-pharmacokinetic-parameters-of-dexamethasone-following-administr-peer-reviewed-fulltext-article-OPTHhttps://doaj.org/toc/1177-5483Charles 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 assessmentsBlizzard CMcLaurin EBDriscoll ASilva FQVantipalli SMetzinger JLGoldstein MHDove Medical Pressarticleintracanalicular dexamethasoneplasma pharmacokineticssustained-release insertsafety assessmentsOphthalmologyRE1-994ENClinical Ophthalmology, Vol Volume 15, Pp 2055-2061 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	intracanalicular dexamethasone plasma pharmacokinetics sustained-release insert safety assessments Ophthalmology RE1-994
spellingShingle	intracanalicular dexamethasone plasma pharmacokinetics sustained-release insert safety assessments Ophthalmology RE1-994 Blizzard C McLaurin EB Driscoll A Silva FQ Vantipalli S Metzinger JL Goldstein MH Plasma Pharmacokinetic Parameters of Dexamethasone Following Administration of a Dexamethasone Intracanalicular Insert in Healthy Adults
description	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
format	article
author	Blizzard C McLaurin EB Driscoll A Silva FQ Vantipalli S Metzinger JL Goldstein MH
author_facet	Blizzard C McLaurin EB Driscoll A Silva FQ Vantipalli S Metzinger JL Goldstein MH
author_sort	Blizzard C
title	Plasma Pharmacokinetic Parameters of Dexamethasone Following Administration of a Dexamethasone Intracanalicular Insert in Healthy Adults
title_short	Plasma Pharmacokinetic Parameters of Dexamethasone Following Administration of a Dexamethasone Intracanalicular Insert in Healthy Adults
title_full	Plasma Pharmacokinetic Parameters of Dexamethasone Following Administration of a Dexamethasone Intracanalicular Insert in Healthy Adults
title_fullStr	Plasma Pharmacokinetic Parameters of Dexamethasone Following Administration of a Dexamethasone Intracanalicular Insert in Healthy Adults
title_full_unstemmed	Plasma Pharmacokinetic Parameters of Dexamethasone Following Administration of a Dexamethasone Intracanalicular Insert in Healthy Adults
title_sort	plasma pharmacokinetic parameters of dexamethasone following administration of a dexamethasone intracanalicular insert in healthy adults
publisher	Dove Medical Press
publishDate	2021
url	https://doaj.org/article/a3d1044738c540a98e4e2930dfaa6914
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Plasma Pharmacokinetic Parameters of Dexamethasone Following Administration of a Dexamethasone Intracanalicular Insert in Healthy Adults

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