Topical and systemic absorption in delivery of dexamethasone to the anterior and posterior segments of the eye

Abstract

ABSTRACT.Purpose: This study aimed to: (1) determine the relative efficiencies of topical and systemic absorption of drugs delivered by eyedrops to the anterior and posterior segments of the eye; (2) establish whether dexamethasone-cyclodextrin eyedrops deliver significant levels of drug to the retina and vitreous in the rabbit eye, and (3) compare systemic absorption following topical application to the eye versus intranasal or intravenous delivery. Methods: In order to distinguish between topical and systemic absorption in the eye, we applied 0.5% dexamethasone-cyclodextrin eyedrops to one (study) eye of rabbits and not to the contralateral (control) eye. Drug levels were measured in each eye. The study eye showed the result of the combination of topical and systemic absorption, whereas the control eye showed the result of systemic absorption only. Systemic absorption was also examined after intranasal and intravenous administration of the same dose of dexamethasone. Results: In the aqueous humour dexamethasone levels were 170 ± 76 ng ⁄ g (mean ± standard deviation) in the study eye and 6 ± 2 ng ⁄ g in the control eye. Similar ratios were seen in the iris and ciliary body. In the retina the dexamethasone level was 33 ± 7 ng ⁄ g in the study eye and 14 ± 3 ng ⁄ g in the control eye. Similar ratios were seen in the vitreous humour. Systemic absorption was similar from ocular, intranasal and intravenous administration. Conclusions: Absorption after topical application dominates in the anterior segment. Topical absorption also plays a significant role in delivering dexamethasone to the posterior segment of the rabbit eye. In medication administered to the retina, 40% of the drug reaches the retina via the systemic route and 60% via topical penetration. Dexamethasone-cyclodextrin eyedrops deliver a significant amount of drug to the rabbit retina.

Corneal permeation properties of a charged lipid nanoparticle carrier containing dexamethasone

“…18 For diseases requiring long-term drug administration such as those of the retina and vitreous body, a dexamethasone/cyclodextrin mixture applied to the ocular surface increased retinal penetration two-fold relative to systemic administration. 19 In situ gels are a novel type of ophthalmic drug delivery system with a longer retention time than that of existing approaches, and they reduce administration frequency and improve bioavailability. In vivo studies have shown that a temperature-sensitive chitosan hydrogel administered as ocular drops had high penetration and sustained release over 12 h while reducing intraocular pressure.…”

Herpes zoster infection after an uncomplicated cataract surgery: A case report

“…Ocular steroids can be available in the systemic circulation and can cause systemic adverse effects. In a study, when the identical doses of steroid were administrated intravenously, intranasally and topically in the conjunctiva, the rates of systemic absorption have been found similar (7). Also, it has been previously reported that topical steroid eye drops may trigger the manifestation of HZ infection (8).…”

Drug Penetration of the Posterior Eye Tissues after Topical Instillation: In Vivo and in Silico Simulation

“…Some studies have indicated that drugs may effectively reach the retina after topical administration. 10) It is important to investigate the detailed pharmacokinetics of the posterior eye tissues with respect to the concentration distribution of drugs.…”