Ocular pharmacokinetics and tolerability of bimatoprost ophthalmic solutions administered once or twice daily in rabbits, and clinical dosing implications

Jie Shen,1 Margot L Goodkin,2 Warren Tong,2 Mayssa Attar3 1Clinical Pharmacology, 2Clinical Development, 3Clinical Pharmacology, Metabolism and Immunology, Allergan plc, Irvine, CA, USA Purpose: Fixed-combination medications can benefit patients requiring multiple agents to lower their intraocular...

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Autores principales:	Shen J, Goodkin ML, Tong W, Attar M
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	Bimatoprost pharmacokinetics glaucoma intraocular pressure hyperemia Ophthalmology RE1-994
Acceso en línea:	https://doaj.org/article/8e4ef6615b574babb232eb66733157da
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spelling	oai:doaj.org-article:8e4ef6615b574babb232eb66733157da2021-12-02T03:43:56ZOcular pharmacokinetics and tolerability of bimatoprost ophthalmic solutions administered once or twice daily in rabbits, and clinical dosing implications1177-5483https://doaj.org/article/8e4ef6615b574babb232eb66733157da2017-09-01T00:00:00Zhttps://www.dovepress.com/ocular-pharmacokinetics-and-tolerability-of-bimatoprost-ophthalmic-sol-peer-reviewed-article-OPTHhttps://doaj.org/toc/1177-5483Jie Shen,1 Margot L Goodkin,2 Warren Tong,2 Mayssa Attar3 1Clinical Pharmacology, 2Clinical Development, 3Clinical Pharmacology, Metabolism and Immunology, Allergan plc, Irvine, CA, USA Purpose: Fixed-combination medications can benefit patients requiring multiple agents to lower their intraocular pressure (IOP), but combining agents with complementary mechanisms of action is challenging if their dosing frequency differs. This study compares in vivo pharmacokinetic and ocular tolerability of bimatoprost 0.01% ophthalmic solutions dosed once or twice daily. Reports of twice-daily dosing in glaucoma patients are also reviewed.Methods: New Zealand White rabbits were administered bimatoprost 0.01% monotherapy or fixed-combination bimatoprost 0.01%/brimonidine 0.1%, once or twice daily in both eyes for 4 days. Ocular tissues were harvested and analyzed by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters calculated included maximum observed concentration, time to maximum concentration, and area under the concentration-time curve.Results: Due to extensive metabolism, bimatoprost concentration was below the quantitation limit by 1 hour post-dose in all samples. Bimatoprost acid exposure, however, could be measured up to 6–8 hours post-dose and was similar in the aqueous humor and iris-ciliary body (pharmacological site of action) of animals treated once or twice daily with either bimatoprost 0.01% or fixed-combination bimatoprost 0.01%/brimonidine 0.1%. Increasing dosage frequency in rabbits did not raise the incidence of drug-related conjunctival hyperemia (most common adverse event associated with bimatoprost use in humans), suggesting comparable ocular tolerability of the once- and twice-daily regimens for each formulation.Conclusion: Bimatoprost 0.01% administered once or twice daily as monotherapy and in fixed-combination with brimonidine 0.1% in rabbits show similar pharmacokinetic profiles of bimatoprost acid, especially in the iris-ciliary body. Key findings from previous clinical studies suggest that by varying the concentration of benzalkonium chloride (a preservative with corneal penetration-enhancing properties), formulations of bimatoprost 0.01% can be administered once or twice daily. These findings support development of bimatoprost 0.01%-based fixed-dose combination therapies administered twice daily for patients who require multiple adjunctive medications to control their IOP. Keywords: bimatoprost, pharmacokinetics, glaucoma, intraocular pressure, hyperemiaShen JGoodkin MLTong WAttar MDove Medical PressarticleBimatoprostpharmacokineticsglaucomaintraocular pressurehyperemiaOphthalmologyRE1-994ENClinical Ophthalmology, Vol Volume 11, Pp 1761-1767 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Bimatoprost pharmacokinetics glaucoma intraocular pressure hyperemia Ophthalmology RE1-994
spellingShingle	Bimatoprost pharmacokinetics glaucoma intraocular pressure hyperemia Ophthalmology RE1-994 Shen J Goodkin ML Tong W Attar M Ocular pharmacokinetics and tolerability of bimatoprost ophthalmic solutions administered once or twice daily in rabbits, and clinical dosing implications
description	Jie Shen,1 Margot L Goodkin,2 Warren Tong,2 Mayssa Attar3 1Clinical Pharmacology, 2Clinical Development, 3Clinical Pharmacology, Metabolism and Immunology, Allergan plc, Irvine, CA, USA Purpose: Fixed-combination medications can benefit patients requiring multiple agents to lower their intraocular pressure (IOP), but combining agents with complementary mechanisms of action is challenging if their dosing frequency differs. This study compares in vivo pharmacokinetic and ocular tolerability of bimatoprost 0.01% ophthalmic solutions dosed once or twice daily. Reports of twice-daily dosing in glaucoma patients are also reviewed.Methods: New Zealand White rabbits were administered bimatoprost 0.01% monotherapy or fixed-combination bimatoprost 0.01%/brimonidine 0.1%, once or twice daily in both eyes for 4 days. Ocular tissues were harvested and analyzed by liquid chromatography-tandem mass spectrometry. The pharmacokinetic parameters calculated included maximum observed concentration, time to maximum concentration, and area under the concentration-time curve.Results: Due to extensive metabolism, bimatoprost concentration was below the quantitation limit by 1 hour post-dose in all samples. Bimatoprost acid exposure, however, could be measured up to 6–8 hours post-dose and was similar in the aqueous humor and iris-ciliary body (pharmacological site of action) of animals treated once or twice daily with either bimatoprost 0.01% or fixed-combination bimatoprost 0.01%/brimonidine 0.1%. Increasing dosage frequency in rabbits did not raise the incidence of drug-related conjunctival hyperemia (most common adverse event associated with bimatoprost use in humans), suggesting comparable ocular tolerability of the once- and twice-daily regimens for each formulation.Conclusion: Bimatoprost 0.01% administered once or twice daily as monotherapy and in fixed-combination with brimonidine 0.1% in rabbits show similar pharmacokinetic profiles of bimatoprost acid, especially in the iris-ciliary body. Key findings from previous clinical studies suggest that by varying the concentration of benzalkonium chloride (a preservative with corneal penetration-enhancing properties), formulations of bimatoprost 0.01% can be administered once or twice daily. These findings support development of bimatoprost 0.01%-based fixed-dose combination therapies administered twice daily for patients who require multiple adjunctive medications to control their IOP. Keywords: bimatoprost, pharmacokinetics, glaucoma, intraocular pressure, hyperemia
format	article
author	Shen J Goodkin ML Tong W Attar M
author_facet	Shen J Goodkin ML Tong W Attar M
author_sort	Shen J
title	Ocular pharmacokinetics and tolerability of bimatoprost ophthalmic solutions administered once or twice daily in rabbits, and clinical dosing implications
title_short	Ocular pharmacokinetics and tolerability of bimatoprost ophthalmic solutions administered once or twice daily in rabbits, and clinical dosing implications
title_full	Ocular pharmacokinetics and tolerability of bimatoprost ophthalmic solutions administered once or twice daily in rabbits, and clinical dosing implications
title_fullStr	Ocular pharmacokinetics and tolerability of bimatoprost ophthalmic solutions administered once or twice daily in rabbits, and clinical dosing implications
title_full_unstemmed	Ocular pharmacokinetics and tolerability of bimatoprost ophthalmic solutions administered once or twice daily in rabbits, and clinical dosing implications
title_sort	ocular pharmacokinetics and tolerability of bimatoprost ophthalmic solutions administered once or twice daily in rabbits, and clinical dosing implications
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/8e4ef6615b574babb232eb66733157da
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Ocular pharmacokinetics and tolerability of bimatoprost ophthalmic solutions administered once or twice daily in rabbits, and clinical dosing implications

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