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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

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. Commer...

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Detalles Bibliográficos
Autores principales: Sheppard, John D., Cockrum, Paul C., Justice, Angela, Jasek, Mark C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Healthcare 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5997598/
https://www.ncbi.nlm.nih.gov/pubmed/29761367
http://dx.doi.org/10.1007/s40123-018-0130-1
Descripción
Sumario: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(0.5–24h)), maximum concentration (C(max)), and time to maximum concentration (T(max)) 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(max) 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.