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Pharmacokinetics of Azithromycin, Levofloxacin, and Ofloxacin in Rabbit Extraocular Tissues After Ophthalmic Administration

INTRODUCTION: Azithromycin demonstrates high tissue distribution and prolonged elimination half-life. In this study, we monitored the pharmacokinetics of a single ophthalmic administration of 1% azithromycin ophthalmic solution containing polycarbophil in the extraocular tissues, including the eyeli...

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Autores principales: Sakai, Tatsuya, Shinno, Keisuke, Kurata, Masaaki, Kawamura, Akio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Healthcare 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858417/
https://www.ncbi.nlm.nih.gov/pubmed/31372937
http://dx.doi.org/10.1007/s40123-019-00205-0
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author Sakai, Tatsuya
Shinno, Keisuke
Kurata, Masaaki
Kawamura, Akio
author_facet Sakai, Tatsuya
Shinno, Keisuke
Kurata, Masaaki
Kawamura, Akio
author_sort Sakai, Tatsuya
collection PubMed
description INTRODUCTION: Azithromycin demonstrates high tissue distribution and prolonged elimination half-life. In this study, we monitored the pharmacokinetics of a single ophthalmic administration of 1% azithromycin ophthalmic solution containing polycarbophil in the extraocular tissues, including the eyelid, and compared it with that of two commercial ophthalmic products, 1.5% levofloxacin ophthalmic solution and 0.3% ofloxacin ophthalmic ointment. METHODS: Rabbits were treated with either a single topical administration of 1% azithromycin ophthalmic solution, 1.5% levofloxacin ophthalmic solution, or 0.3% ofloxacin ophthalmic ointment. The eyelid, conjunctiva, and cornea were collected at 0.25, 0.5, 1, 2, 4, 8, and 24 h post-administration. Tissue samples were pretreated for drug concentration measurements by ultra-performance liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were determined by non-compartmental analysis. RESULTS: Azithromycin was rapidly absorbed, and its levels remained near the observed maximum concentrations for up to 24 h post-administration in all tissue. In contrast, extraocular tissue concentrations of levofloxacin and ofloxacin decreased with time. The maximum concentrations of azithromycin, levofloxacin, and ofloxacin were 35.6, 34.1, and 55.1 µg/g in the eyelid, 44.2, 46.8, and 20.4 µg/g in the conjunctiva, and 79.9, 18.0, and 2.21 µg/g in the cornea, respectively. The values of the area under the curve from 0 to 24 h after administration of azithromycin, levofloxacin, and ofloxacin were 602, 58.5, and 267 µg·h/g in the eyelid, 837, 43.2, and 51.9 µg·h/g in the conjunctiva, and 1250, 26.4, and 5.46 µg h/g in the cornea, respectively. CONCLUSION: The drug concentrations of azithromycin and levofloxacin were relatively comparable among the extraocular tissues following topical administration of the respective ophthalmic solutions, whereas the concentrations of ofloxacin varied following dosing of its ophthalmic ointment. The slow elimination profile in any extraocular tissue of rabbits was unique to azithromycin, and led to the demonstration of high exposures of azithromycin in all extraocular tissues after ophthalmic administration. FUNDING: This research and Rapid Service Fees were supported by Senju Pharmaceutical Co., Ltd.
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spelling pubmed-68584172019-12-03 Pharmacokinetics of Azithromycin, Levofloxacin, and Ofloxacin in Rabbit Extraocular Tissues After Ophthalmic Administration Sakai, Tatsuya Shinno, Keisuke Kurata, Masaaki Kawamura, Akio Ophthalmol Ther Original Research INTRODUCTION: Azithromycin demonstrates high tissue distribution and prolonged elimination half-life. In this study, we monitored the pharmacokinetics of a single ophthalmic administration of 1% azithromycin ophthalmic solution containing polycarbophil in the extraocular tissues, including the eyelid, and compared it with that of two commercial ophthalmic products, 1.5% levofloxacin ophthalmic solution and 0.3% ofloxacin ophthalmic ointment. METHODS: Rabbits were treated with either a single topical administration of 1% azithromycin ophthalmic solution, 1.5% levofloxacin ophthalmic solution, or 0.3% ofloxacin ophthalmic ointment. The eyelid, conjunctiva, and cornea were collected at 0.25, 0.5, 1, 2, 4, 8, and 24 h post-administration. Tissue samples were pretreated for drug concentration measurements by ultra-performance liquid chromatography-tandem mass spectrometry. Pharmacokinetic parameters were determined by non-compartmental analysis. RESULTS: Azithromycin was rapidly absorbed, and its levels remained near the observed maximum concentrations for up to 24 h post-administration in all tissue. In contrast, extraocular tissue concentrations of levofloxacin and ofloxacin decreased with time. The maximum concentrations of azithromycin, levofloxacin, and ofloxacin were 35.6, 34.1, and 55.1 µg/g in the eyelid, 44.2, 46.8, and 20.4 µg/g in the conjunctiva, and 79.9, 18.0, and 2.21 µg/g in the cornea, respectively. The values of the area under the curve from 0 to 24 h after administration of azithromycin, levofloxacin, and ofloxacin were 602, 58.5, and 267 µg·h/g in the eyelid, 837, 43.2, and 51.9 µg·h/g in the conjunctiva, and 1250, 26.4, and 5.46 µg h/g in the cornea, respectively. CONCLUSION: The drug concentrations of azithromycin and levofloxacin were relatively comparable among the extraocular tissues following topical administration of the respective ophthalmic solutions, whereas the concentrations of ofloxacin varied following dosing of its ophthalmic ointment. The slow elimination profile in any extraocular tissue of rabbits was unique to azithromycin, and led to the demonstration of high exposures of azithromycin in all extraocular tissues after ophthalmic administration. FUNDING: This research and Rapid Service Fees were supported by Senju Pharmaceutical Co., Ltd. Springer Healthcare 2019-08-01 2019-12 /pmc/articles/PMC6858417/ /pubmed/31372937 http://dx.doi.org/10.1007/s40123-019-00205-0 Text en © The Author(s) 2019 https://creativecommons.org/licenses/by-nc/4.0/This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) ), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
spellingShingle Original Research
Sakai, Tatsuya
Shinno, Keisuke
Kurata, Masaaki
Kawamura, Akio
Pharmacokinetics of Azithromycin, Levofloxacin, and Ofloxacin in Rabbit Extraocular Tissues After Ophthalmic Administration
title Pharmacokinetics of Azithromycin, Levofloxacin, and Ofloxacin in Rabbit Extraocular Tissues After Ophthalmic Administration
title_full Pharmacokinetics of Azithromycin, Levofloxacin, and Ofloxacin in Rabbit Extraocular Tissues After Ophthalmic Administration
title_fullStr Pharmacokinetics of Azithromycin, Levofloxacin, and Ofloxacin in Rabbit Extraocular Tissues After Ophthalmic Administration
title_full_unstemmed Pharmacokinetics of Azithromycin, Levofloxacin, and Ofloxacin in Rabbit Extraocular Tissues After Ophthalmic Administration
title_short Pharmacokinetics of Azithromycin, Levofloxacin, and Ofloxacin in Rabbit Extraocular Tissues After Ophthalmic Administration
title_sort pharmacokinetics of azithromycin, levofloxacin, and ofloxacin in rabbit extraocular tissues after ophthalmic administration
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6858417/
https://www.ncbi.nlm.nih.gov/pubmed/31372937
http://dx.doi.org/10.1007/s40123-019-00205-0
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