Ocular pharmacokinetics of bimatoprost formulated in DuraSite compared to bimatoprost 0.03% ophthalmic solution in pigmented rabbit eyes

Afshin Shafiee,1 Lyle M Bowman,2 Eddie Hou,2 Kamran Hosseini1,3 1Preclinical, 2Development, 3Clinical, InSite Vision, Alameda, CA, USA Purpose: To compare the aqueous humor (AH) and iris-ciliary body (ICB) concentration of bimatoprost in rabbit eyes treated with ISV-215 (0.03% bimatoprost formulated...

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Autores principales:	Shafiee A, Bowman LM, Hou E, Hosseini K
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2013
Materias:	Ophthalmology RE1-994
Acceso en línea:	https://doaj.org/article/159b2c3b7cfe46f3b27c4d8bc9e02435
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spelling	oai:doaj.org-article:159b2c3b7cfe46f3b27c4d8bc9e024352021-12-02T07:14:36ZOcular pharmacokinetics of bimatoprost formulated in DuraSite compared to bimatoprost 0.03% ophthalmic solution in pigmented rabbit eyes1177-54671177-5483https://doaj.org/article/159b2c3b7cfe46f3b27c4d8bc9e024352013-07-01T00:00:00Zhttp://www.dovepress.com/ocular-pharmacokinetics-of-bimatoprost-formulated-in-durasite-compared-a13865https://doaj.org/toc/1177-5467https://doaj.org/toc/1177-5483Afshin Shafiee,1 Lyle M Bowman,2 Eddie Hou,2 Kamran Hosseini1,3 1Preclinical, 2Development, 3Clinical, InSite Vision, Alameda, CA, USA Purpose: To compare the aqueous humor (AH) and iris-ciliary body (ICB) concentration of bimatoprost in rabbit eyes treated with ISV-215 (0.03% bimatoprost formulated in DuraSite) with the marketed product bimatoprost 0.03% ophthalmic solution. Methods: The left eye of rabbits received a single topical instillation of either ISV-215 (n = 32 eyes) or bimatoprost 0.03% (n = 32 eyes). At predetermined time points, levels of bimatoprost and bimatoprost acid in the AH and the ICB were quantified by HPLC-MS/MS. Results: Both bimatoprost and bimatoprost acid were detected in the AH and the ICB within 15 minutes of dosing. Bimatoprost acid concentrations in both compartments were markedly higher than bimatoprost. There was a statistically significant (P < 0.01) increase in the concentration of the prodrug in the AH and its acid form in the ICB in animals treated with ISV-215 compared to bimatoprost 0.03%. In the ISV-215-treated rabbit eyes, the highest concentrations of bimatoprost and bimatoprost acid were in the ICB and AH, respectively, while in the bimatoprost 0.03%-treated eyes, no differences in the drug content of the selected ocular tissues were observed. Conclusions: Bimatoprost 0.03% formulated in DuraSite has superior ocular distribution and area under the curve compared to bimatoprost 0.03% in rabbit eyes. This improvement in the pharmacokinetic parameters of ISV-215 may provide us with a better platform to optimize a bimatoprost formulation that offers the same degree of efficacy in lowering intraocular pressure and improved therapeutic index in glaucomatous patients by lessening the ocular side effects associated with long-term use of topical prostaglandin F2α analogs. Keywords: drug delivery, intraocular pressure, glaucoma, aqueous humor, prostaglandin (PGF2α) analogsShafiee ABowman LMHou EHosseini KDove Medical PressarticleOphthalmologyRE1-994ENClinical Ophthalmology, Vol 2013, Iss default, Pp 1549-1556 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Ophthalmology RE1-994
spellingShingle	Ophthalmology RE1-994 Shafiee A Bowman LM Hou E Hosseini K Ocular pharmacokinetics of bimatoprost formulated in DuraSite compared to bimatoprost 0.03% ophthalmic solution in pigmented rabbit eyes
description	Afshin Shafiee,1 Lyle M Bowman,2 Eddie Hou,2 Kamran Hosseini1,3 1Preclinical, 2Development, 3Clinical, InSite Vision, Alameda, CA, USA Purpose: To compare the aqueous humor (AH) and iris-ciliary body (ICB) concentration of bimatoprost in rabbit eyes treated with ISV-215 (0.03% bimatoprost formulated in DuraSite) with the marketed product bimatoprost 0.03% ophthalmic solution. Methods: The left eye of rabbits received a single topical instillation of either ISV-215 (n = 32 eyes) or bimatoprost 0.03% (n = 32 eyes). At predetermined time points, levels of bimatoprost and bimatoprost acid in the AH and the ICB were quantified by HPLC-MS/MS. Results: Both bimatoprost and bimatoprost acid were detected in the AH and the ICB within 15 minutes of dosing. Bimatoprost acid concentrations in both compartments were markedly higher than bimatoprost. There was a statistically significant (P < 0.01) increase in the concentration of the prodrug in the AH and its acid form in the ICB in animals treated with ISV-215 compared to bimatoprost 0.03%. In the ISV-215-treated rabbit eyes, the highest concentrations of bimatoprost and bimatoprost acid were in the ICB and AH, respectively, while in the bimatoprost 0.03%-treated eyes, no differences in the drug content of the selected ocular tissues were observed. Conclusions: Bimatoprost 0.03% formulated in DuraSite has superior ocular distribution and area under the curve compared to bimatoprost 0.03% in rabbit eyes. This improvement in the pharmacokinetic parameters of ISV-215 may provide us with a better platform to optimize a bimatoprost formulation that offers the same degree of efficacy in lowering intraocular pressure and improved therapeutic index in glaucomatous patients by lessening the ocular side effects associated with long-term use of topical prostaglandin F2α analogs. Keywords: drug delivery, intraocular pressure, glaucoma, aqueous humor, prostaglandin (PGF2α) analogs
format	article
author	Shafiee A Bowman LM Hou E Hosseini K
author_facet	Shafiee A Bowman LM Hou E Hosseini K
author_sort	Shafiee A
title	Ocular pharmacokinetics of bimatoprost formulated in DuraSite compared to bimatoprost 0.03% ophthalmic solution in pigmented rabbit eyes
title_short	Ocular pharmacokinetics of bimatoprost formulated in DuraSite compared to bimatoprost 0.03% ophthalmic solution in pigmented rabbit eyes
title_full	Ocular pharmacokinetics of bimatoprost formulated in DuraSite compared to bimatoprost 0.03% ophthalmic solution in pigmented rabbit eyes
title_fullStr	Ocular pharmacokinetics of bimatoprost formulated in DuraSite compared to bimatoprost 0.03% ophthalmic solution in pigmented rabbit eyes
title_full_unstemmed	Ocular pharmacokinetics of bimatoprost formulated in DuraSite compared to bimatoprost 0.03% ophthalmic solution in pigmented rabbit eyes
title_sort	ocular pharmacokinetics of bimatoprost formulated in durasite compared to bimatoprost 0.03% ophthalmic solution in pigmented rabbit eyes
publisher	Dove Medical Press
publishDate	2013
url	https://doaj.org/article/159b2c3b7cfe46f3b27c4d8bc9e02435
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Ocular pharmacokinetics of bimatoprost formulated in DuraSite compared to bimatoprost 0.03% ophthalmic solution in pigmented rabbit eyes

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