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

Sheppard, John D.; Cockrum, Paul; Justice, Angela; Jasek, Mark C

doi:10.1007/s40123-018-0130-1

Cited by 14 publications

(13 citation statements)

References 21 publications

(20 reference statements)

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“…Similarly, following a single 50-µL topical dose of 14 C-bromfenac 0.07% solution, bromfenac was detected using liquid scintillation chromatography in ocular tissues for up to 24 hrs with a similar distribution as bromfenac 0.09% (single 50-µL dose) 34. In another rabbit PK study comparing the ocular penetration of bromfenac following a QD 40-µL topical dose of either bromfenac 0.075% solution formulated in DuraSite or bromfenac 0.07% solution for a total of 9 days, there were no apparent differences in drug concentrations in either the anterior and posterior ocular tissues as measured by HPLC 46. As expected, bromfenac 0.075% in DuraSite dosed BID (the approved clinical dosing regimen) achieved significantly higher ocular concentrations compared to bromfenac 0.07% dosed QD 46.…”

Section: Introductionmentioning

confidence: 89%

“…In another rabbit PK study comparing the ocular penetration of bromfenac following a QD 40-µL topical dose of either bromfenac 0.075% solution formulated in DuraSite or bromfenac 0.07% solution for a total of 9 days, there were no apparent differences in drug concentrations in either the anterior and posterior ocular tissues as measured by HPLC 46. As expected, bromfenac 0.075% in DuraSite dosed BID (the approved clinical dosing regimen) achieved significantly higher ocular concentrations compared to bromfenac 0.07% dosed QD 46. However, both formulations reached tissue levels in excess of the reported IC 50 for bromfenac.…”

Section: Introductionmentioning

confidence: 98%

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<p>Use of topical bromfenac for treating ocular pain and inflammation beyond cataract surgery: a review of published studies</p>

Schechter¹

2019

OPTH

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Topical ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat postoperative inflammation and pain following cataract surgery and for treatment and prophylaxis of pseudophakic cystoid macular edema (CME). Bromfenac is a brominated NSAID with strong in vitro anti-inflammatory potency. Like other ophthalmic NSAIDs, bromfenac is often used outside of the cataract surgery setting. This paper provides an overview of bromfenac’s preclinical ocular pharmacology and pharmacokinetics, followed by a review of 23 published clinical studies in which various marketed bromfenac formulations were used for conditions other than cataract surgery or pseudophakic CME. These include: post-refractive eye surgery; macular edema associated with diabetes, uveitis, or retinal vein occlusion; inflammation associated with age-related macular degeneration; pain related to intravitreal injections; and other ocular anterior segment and surface disorders with an inflammatory component. The published evidence reviewed supports the safety and effectiveness of bromfenac in these additional ophthalmic indications. Bromfenac was well tolerated when given alone or in combination with intravitreal anti-vascular endothelial growth factor agents, topical corticosteroids, or topical mast-cell stabilizers. The most common adverse event reported was ocular irritation. No serious adverse events (ie, corneal epithelial disorders) were reported, although the majority of studies did not systematically evaluate potential side effects. Corneal complications, such as melts reported with diclofenac and ketorolac, were not observed with bromfenac in the studies. In summary, published study data support the clinical utility of bromfenac in various ocular disorders beyond post-cataract surgery. Additional studies are warranted to further define the potential role of bromfenac ophthalmic solution in clinical practice.

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Section: Introductionmentioning

confidence: 89%

Section: Introductionmentioning

confidence: 98%

<p>Use of topical bromfenac for treating ocular pain and inflammation beyond cataract surgery: a review of published studies</p>

Schechter¹

2019

OPTH

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“…These pivotal reports demonstrate that particle size affects the ocular absorption of dexamethasone [ 7 ] and fluorometholone [ 8 ] from topically instilled suspensions in rabbits. Increased drug absorption from nanosized particles has also been observed [ 13 , 14 , 15 , 16 , 17 , 18 ]. These studies suggest that dissolution of suspended particles plays a role in ocular drug absorption.…”

Section: Introductionmentioning

confidence: 99%

Biopharmaceutics of Topical Ophthalmic Suspensions: Importance of Viscosity and Particle Size in Ocular Absorption of Indomethacin

et al. 2021

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Eye drops of poorly soluble drugs are frequently formulated as suspensions. Bioavailability of suspended drug depends on the retention and dissolution of drug particles in the tear fluid, but these factors are still poorly understood. We investigated seven ocular indomethacin suspensions (experimental suspensions with two particle sizes and three viscosities, one commercial suspension) in physical and biological tests. The median particle size (d50) categories of the experimental suspensions were 0.37–1.33 and 3.12–3.50 µm and their viscosity levels were 1.3, 7.0, and 15 mPa·s. Smaller particle size facilitated ocular absorption of indomethacin to the aqueous humor of albino rabbits. In aqueous humor the AUC values of indomethacin suspensions with different particle sizes, but equal viscosity, differed over a 1.5 to 2.3-fold range. Higher viscosity increased ocular absorption 3.4–4.3-fold for the suspensions with similar particle sizes. Overall, the bioavailability range for the suspensions was about 8-fold. Instillation of larger particles resulted in higher tear fluid AUC values of total indomethacin (suspended and dissolved) as compared to application of smaller particles. Despite these tear fluid AUC values of total indomethacin, instillation of the larger particles resulted in smaller AUC levels of indomethacin in the aqueous humor. This suggests that the small particles yielded higher concentrations of dissolved indomethacin in the tear fluid, thereby leading to improved ocular bioavailability. This new conclusion was supported by ocular pharmacokinetic modeling. Both particle size and viscosity have a significant impact on drug concentrations in the tear fluid and ocular drug bioavailability from topical suspensions. Viscosity and particle size are the key players in the complex interplay of drug retention and dissolution in the tear fluid, thereby defining ocular drug absorption and bioequivalence of ocular suspensions.

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“…The authors postulated that the DuraSite component of bromfenac in DuraSite enhanced ocular penetration throughout both anterior and posterior tissues. 12 The human ocular pharmacokinetic (PK) details of bromfenac in DuraSite have not been published to date. Additionally, there have been no studies to address PK comparisons to Bromday ® (bromfenac ophthalmic solution 0.09%).…”

Section: Introductionmentioning

confidence: 99%

An ex vivo human aqueous humor-concentration comparison of two commercial bromfenac formulations

TR¹,

Smyth-Medina²,

Cockrum³

2018

OPTH

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PurposeThe purpose of this study was to quantify the concentration of bromfenac in the aqueous humor utilizing high-performance liquid chromatography mass spectrometry between two commercial nonsteroidal anti-inflammatory drugs, using aqueous humor concentrations to characterize pharmacokinetic proportional differences between 0.075% bromfenac ophthalmic solution in DuraSite (BromSite®) and 0.09% bromfenac ophthalmic solution (Bromday®).MethodsIn this multicenter, randomized, double-masked, two-arm, parallel-group, comparative, Phase II clinical trial, subjects were assigned to receive bromfenac in DuraSite or bromfenac ophthalmic solution in a 1:1 ratio. One drop of the masked test article was instilled into the study eye once a day for 2 days prior to and 3 hours prior (last instillation) to the subject’s cataract surgery. Aqueous humor samples were collected upon initial cataract incision for analysis of bromfenac levels. The primary end point was aqueous humor concentration of bromfenac at Day 3, at the initiation of cataract surgery. Aqueous humor samples were collected and analyzed for bromfenac levels.ResultsA total of 60 subjects completed the study, 30 in each group. The mean bromfenac aqueous humor concentration in subjects who received bromfenac in DuraSite was more than twice (49.33±41.87 ng/mL, P=0.004) that of subjects who received bromfenac ophthalmic solution (23.65±16.31 ng/mL) after three doses.ConclusionMean bromfenac aqueous humor concentration in subjects receiving the DuraSite-containing bromfenac in DuraSite (0.075%) was significantly higher compared to subjects receiving bromfenac ophthalmic solution (0.09%) after 3 days of dosing.

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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

Cited by 14 publications

References 21 publications

<p>Use of topical bromfenac for treating ocular pain and inflammation beyond cataract surgery: a review of published studies</p>

<p>Use of topical bromfenac for treating ocular pain and inflammation beyond cataract surgery: a review of published studies</p>

Biopharmaceutics of Topical Ophthalmic Suspensions: Importance of Viscosity and Particle Size in Ocular Absorption of Indomethacin

An ex vivo human aqueous humor-concentration comparison of two commercial bromfenac formulations

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