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In Vivo Pharmacokinetics of Bromfenac Ophthalmic Solution 0.075%, Bromfenac Ophthalmic Solution 0.07%, and Nepafenac/Amfenac Ophthalmic Suspension 0.3% in Rabbits

Overview
Journal Ophthalmol Ther
Specialty Ophthalmology
Date 2018 May 16
PMID 29761367
Citations 5
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Abstract

Introduction: Little is known of the ocular distribution characteristics of currently branded non-steroidal anti-inflammatory drugs (NSAIDs) in the United States. This study was designed to predict the ocular bioavailability characteristics in humans using Dutch Belted rabbits as a surrogate. Commercially available, topically-applied NSAIDs containing bromfenac or nepafenac/amfenac were evaluated.

Methods: 126 healthy adult Dutch Belted rabbits were randomly assigned to three treatment cohorts (BromSite twice daily [BID] in the right eye, BromSite once daily [QD] in the right eye, Prolensa QD in the right eye and Ilevro™ QD in the left eye) and 7 post-dosing time points (0.5, 1, 2, 4, 8, 12, 24 h after final instillation). The study eyes received 40 µL of the assigned drug for a consecutive 9 days. Samples of aqueous humor, iris-ciliary body, choroid, sclera, and retina were harvested from the study eyes at the assigned time point after the last dose on the 9th day. NSAID content in ocular tissues was analyzed using high-performance liquid chromatography (HPLC), and area under the curve (AUC), maximum concentration (C), and time to maximum concentration (T) were determined.

Results: Peak NSAID concentrations were reached within 1-3 h in the anterior segment and within 1-3 h in the posterior segment after last dose. Throughout the ocular tissues, both AUC and C for BromSite (BID and QD) were consistently higher than respective NSAID concentrations of Prolensa QD and Ilevro QD. When comparing BromSite BID to QD, the BID regimen produced generally higher but statistically similar bromfenac concentrations throughout the ocular tissues except in the aqueous humor and iris-ciliary body, where the AUC BID was statistically significantly higher with BromSite BID.

Conclusion: As a surrogate to human ocular bioavailability, BromSite demonstrated significantly greater NSAID compared to Prolensa QD and Ilevro QD. The DuraSite component of BromSite appears to enhance ocular penetration throughout both anterior and posterior tissues.

Funding: Sun Pharmaceutical Industries Ltd.

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