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dc.contributor.authorSeal, JR
dc.contributor.authorRobinson, MR
dc.contributor.authorBurke, J
dc.contributor.authorBejanian, M
dc.contributor.authorCoote, M
dc.contributor.authorAttar, M
dc.date.accessioned2020-12-10T01:43:44Z
dc.date.available2020-12-10T01:43:44Z
dc.date.issued2019-01
dc.identifier.citationSeal, J. R., Robinson, M. R., Burke, J., Bejanian, M., Coote, M. & Attar, M. (2019). Intracameral Sustained-Release Bimatoprost Implant Delivers Bimatoprost to Target Tissues with Reduced Drug Exposure to Off-Target Tissues.. J Ocul Pharmacol Ther, 35 (1), pp.50-57. https://doi.org/10.1089/jop.2018.0067.
dc.identifier.issn1080-7683
dc.identifier.urihttp://hdl.handle.net/11343/253777
dc.description.abstractPURPOSE: To explore the ocular distribution of bimatoprost after intracameral administration of a biodegradable sustained-release bimatoprost implant (Bimatoprost SR) versus repeated topical administration of bimatoprost 0.03% ophthalmic solution in dogs. Bimatoprost SR and topical bimatoprost 0.03% previously were shown to have similar intraocular pressure-lowering effects in humans in a phase 1/2 clinical trial. METHODS: Twenty-four beagle dogs received either once-daily topical bimatoprost 0.03% for 7 days or a bilateral intracameral administration of Bimatoprost SR (15 μg). At predetermined time points, ocular tissues were collected and concentrations of bimatoprost and bimatoprost acid were quantified using liquid chromatography-tandem mass spectrometry. RESULTS: Bimatoprost SR administration enhanced delivery of study drug to a site of action [iris-ciliary body (ICB)] compared with topical bimatoprost (Cmax [bimatoprost+bimatoprost acid] = 18,200 and 4.13 ng/g, respectively). However, distribution of drug to tissues associated with prostaglandin analog (PGA)-related side effects (i.e., bulbar conjunctiva, eyelid margins, and periorbital fat) was limited following Bimatoprost SR administration (Cmax [bimatoprost+bimatoprost acid] = BLQ [beneath the limit of quantitation] to 0.354 ng/g) compared with topical dosing (Cmax [bimatoprost+bimatoprost acid] = 36.6-2,110 ng/g). CONCLUSIONS: Bimatoprost SR administration in dogs selectively delivered drug to the ICB with low or undetectable drug levels in ocular surface and extraocular tissues. Use of Bimatoprost SR for glaucoma treatment may reduce the incidence of adverse events typically associated with topical PGAs by targeting bimatoprost delivery to the key site of action of the PGA class and reducing exposure to off-target tissues.
dc.languageeng
dc.publisherMary Ann Liebert Inc
dc.titleIntracameral Sustained-Release Bimatoprost Implant Delivers Bimatoprost to Target Tissues with Reduced Drug Exposure to Off-Target Tissues.
dc.typeJournal Article
dc.identifier.doi10.1089/jop.2018.0067
melbourne.affiliation.departmentOphthalmology (Eye & Ear Hospital)
melbourne.source.titleJournal of Ocular Pharmacology and Therapeutics
melbourne.source.volume35
melbourne.source.issue1
melbourne.source.pages50-57
dc.rights.licenseCC BY
melbourne.elementsid1372431
melbourne.openaccess.pmchttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354606
melbourne.contributor.authorCoote, Michael
dc.identifier.eissn1557-7732
melbourne.accessrightsOpen Access


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