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Paul Cockrum, Angela Justice, Mark C Jasek, John D Sheppard; In Vivo Pharmacokinetics of Bromfenac Ophthalmic Solution 0.075%, Bromfenac Ophthalmic Solution 0.07%, and Nepafenac/Amfenac Ophthalmic Suspension 0.3% in Rabbits. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2662.
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© ARVO (1962-2015); The Authors (2016-present)
An ocular distribution comparison of contemporary branded agents used for ophthalmic surgery has not been reported. Since a human ocular distribution study is not realistic, we tested the ocular bioavailability characteristics in rabbits of branded, commercially available, non-steroidal anti-inflammatory drugs (NSAIDs): BromSite® (bromfenac ophthalmic solution 0.075% in DuraSite®), Prolensa® (bromfenac ophthalmic solution 0.07%), or Ilevro® (nepafenac ophthalmic suspension 0.3%).
NSAID concentration was measured in 126 Dutch Belted rabbits after a multiple dose regimen for 9 days. 3 rabbit cohorts (42 rabbits each; half males; 14-20 weeks of age) were evaluated: Cohort A, BromSite® BID in right eye; Cohort B, BromSite® QD in right eye; Cohort C, Prolensa® QD in right eye/Ilevro™ QD in left eye. On the morning of day 9, all animals received the last dose and collection of tissues (i.e., aqueous humor, iris-ciliary body, choroid, sclera, and retina) was taken based upon group assignment at 0.5, 1, 2, 4, 8, 12, and 24 h after final instillation of the 40 µL dose used throughout the study. The NSAID content in ocular tissues was analyzed using liquid chromatography atmospheric pressure ionization tandem mass spectrometry, and AUC0.5–24h Cmax, and Tmax, were determined.
Peak NSAID concentrations were reached within 1-3 hours in the anterior segment and within 1-3 hours in the posterior segment after last dose. Throughout the ocular tissues, both AUC and Cmax 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. Aqueous humor (A) and retina (B) concentrations are provided.
As a surrogate to human ocular bioavailability, BromSite® demonstrated significantly greater NSAID penetration compared to Prolensa® QD and Ilevro® QD. The DuraSite® component of BromSite® appears to enhance ocular penetration throughout the anterior and posterior tissues.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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