Comparative Assessment of Distribution Characteristics and Ocular Pharmacokinetics of Norvancomycin Between Continuous Topical Ocular Instillation and Hourly Administration of Eye Drop
Wenxiang Lin,1,2 Libei Zhao,1,2 Xuetao Huang,3 Qian Tan,1,2 Manqiang Peng,1,2 Muhammad Ahmad Khan,1,2 Ding Lin1,2 1Aier School of Ophthalmology, Central South University, Changsha, People’s Republic of China; 2Department of Ophthalmology, Changsha Aier Eye Hospital, Changsha, People&rs...
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doaj-9403727f7010452eb22f9380829282692020-11-25T01:13:29ZengDove Medical PressDrug Design, Development and Therapy1177-88812020-02-01Volume 1486787952080Comparative Assessment of Distribution Characteristics and Ocular Pharmacokinetics of Norvancomycin Between Continuous Topical Ocular Instillation and Hourly Administration of Eye DropLin WZhao LHuang XTan QPeng MKhan MALin DWenxiang Lin,1,2 Libei Zhao,1,2 Xuetao Huang,3 Qian Tan,1,2 Manqiang Peng,1,2 Muhammad Ahmad Khan,1,2 Ding Lin1,2 1Aier School of Ophthalmology, Central South University, Changsha, People’s Republic of China; 2Department of Ophthalmology, Changsha Aier Eye Hospital, Changsha, People’s Republic of China; 3Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Ding LinDepartment of Ophthalmology, Changsha Aier Eye Hospital, Aier School of Ophthalmology, Central South University, Changsha, People’s Republic of ChinaTel +86-13787255158Email linding@csu.edu.cnBackground: The aim of this study was to compare the distribution characteristics and ocular pharmacokinetics of norvancomycin (NVCM) in ocular tissues of the anterior segment between continuous topical ocular instillation and hourly administration of eye drop in rabbits.Methods: Sixty rabbits were randomly divided into two groups: continuous topical ocular instillation drug delivery (CTOIDD) group and eye drop (control) group. In the CTOIDD group, NVCM solution (50 mg/mL) was perfused to the ocular surface using the CTOIDD system at 2 mL/h up to 10 h and the same solution was administered at one drop (50 μL) per hour for 10 h in the control group. Animals (N=6 per time-point per group) were humanely killed at 2, 4, 6, 10, and 24 h to analyze their ocular tissues and plasma. The concentrations of NVCM in the conjunctiva, cornea, aqueous humour, iris, ciliary body and plasma were measured by HPLC with photodiode array detector. The pharmacokinetic parameters were calculated by Kinetica 5.1.Results: The highest concentrations of NVCM for the CTOIDD group and control group were 2105.45± 919.89 μg/g and 97.18± 43.14 μg/g in cornea, 3033.92± 1061.95 μg/g and 806.99± 563.02 μg/g in conjunctiva, 1570.19± 402.87 μg/g and 46.93± 23.46 μg/g in iris, 181.94± 47.11 μg/g and 15.38± 4.00 μg/g in ciliary body, 29.78± 4.90 μg/mL and 3.20± 1.48 μg/mL in aqueous humour, and 26.89± 5.57 μg/mL and 1.90± 1.87 μg/mL in plasma, respectively. The mean NVCM levels significantly increased at all time-points in cornea, iris, and ciliary body (p< 0.05) in the CTOIDD group. The AUC0– 24 values in the CTOIDD group were 27,543.70 μg·h/g in cornea, 32,514.48 μg·h/g in conjunctiva, 8631.05 μg·h/g in iris, 2194.36 μg·h/g in ciliary body and 343.9 μg·h/mL in aqueous humour, which were higher than for the eye drop group in all tissues.Conclusion: Since continuous instillation of NVCM with CTOIDD could reach significantly higher concentrations and was sustained for a longer period compared with hourly administration of eye drop, CTOIDD administered NVCM could be a possible method to treat bacterial keratitis.Keywords: topical drug delivery, ocular tissue, anterior segment, area under the curve, rabbit eyehttps://www.dovepress.com/comparative-assessment-of-distribution-characteristics-and-ocular-phar-peer-reviewed-article-DDDTtopical drug deliveryocular tissueanterior segmentarea under the curverabbit eye |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Lin W Zhao L Huang X Tan Q Peng M Khan MA Lin D |
spellingShingle |
Lin W Zhao L Huang X Tan Q Peng M Khan MA Lin D Comparative Assessment of Distribution Characteristics and Ocular Pharmacokinetics of Norvancomycin Between Continuous Topical Ocular Instillation and Hourly Administration of Eye Drop Drug Design, Development and Therapy topical drug delivery ocular tissue anterior segment area under the curve rabbit eye |
author_facet |
Lin W Zhao L Huang X Tan Q Peng M Khan MA Lin D |
author_sort |
Lin W |
title |
Comparative Assessment of Distribution Characteristics and Ocular Pharmacokinetics of Norvancomycin Between Continuous Topical Ocular Instillation and Hourly Administration of Eye Drop |
title_short |
Comparative Assessment of Distribution Characteristics and Ocular Pharmacokinetics of Norvancomycin Between Continuous Topical Ocular Instillation and Hourly Administration of Eye Drop |
title_full |
Comparative Assessment of Distribution Characteristics and Ocular Pharmacokinetics of Norvancomycin Between Continuous Topical Ocular Instillation and Hourly Administration of Eye Drop |
title_fullStr |
Comparative Assessment of Distribution Characteristics and Ocular Pharmacokinetics of Norvancomycin Between Continuous Topical Ocular Instillation and Hourly Administration of Eye Drop |
title_full_unstemmed |
Comparative Assessment of Distribution Characteristics and Ocular Pharmacokinetics of Norvancomycin Between Continuous Topical Ocular Instillation and Hourly Administration of Eye Drop |
title_sort |
comparative assessment of distribution characteristics and ocular pharmacokinetics of norvancomycin between continuous topical ocular instillation and hourly administration of eye drop |
publisher |
Dove Medical Press |
series |
Drug Design, Development and Therapy |
issn |
1177-8881 |
publishDate |
2020-02-01 |
description |
Wenxiang Lin,1,2 Libei Zhao,1,2 Xuetao Huang,3 Qian Tan,1,2 Manqiang Peng,1,2 Muhammad Ahmad Khan,1,2 Ding Lin1,2 1Aier School of Ophthalmology, Central South University, Changsha, People’s Republic of China; 2Department of Ophthalmology, Changsha Aier Eye Hospital, Changsha, People’s Republic of China; 3Department of Ophthalmology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of ChinaCorrespondence: Ding LinDepartment of Ophthalmology, Changsha Aier Eye Hospital, Aier School of Ophthalmology, Central South University, Changsha, People’s Republic of ChinaTel +86-13787255158Email linding@csu.edu.cnBackground: The aim of this study was to compare the distribution characteristics and ocular pharmacokinetics of norvancomycin (NVCM) in ocular tissues of the anterior segment between continuous topical ocular instillation and hourly administration of eye drop in rabbits.Methods: Sixty rabbits were randomly divided into two groups: continuous topical ocular instillation drug delivery (CTOIDD) group and eye drop (control) group. In the CTOIDD group, NVCM solution (50 mg/mL) was perfused to the ocular surface using the CTOIDD system at 2 mL/h up to 10 h and the same solution was administered at one drop (50 μL) per hour for 10 h in the control group. Animals (N=6 per time-point per group) were humanely killed at 2, 4, 6, 10, and 24 h to analyze their ocular tissues and plasma. The concentrations of NVCM in the conjunctiva, cornea, aqueous humour, iris, ciliary body and plasma were measured by HPLC with photodiode array detector. The pharmacokinetic parameters were calculated by Kinetica 5.1.Results: The highest concentrations of NVCM for the CTOIDD group and control group were 2105.45± 919.89 μg/g and 97.18± 43.14 μg/g in cornea, 3033.92± 1061.95 μg/g and 806.99± 563.02 μg/g in conjunctiva, 1570.19± 402.87 μg/g and 46.93± 23.46 μg/g in iris, 181.94± 47.11 μg/g and 15.38± 4.00 μg/g in ciliary body, 29.78± 4.90 μg/mL and 3.20± 1.48 μg/mL in aqueous humour, and 26.89± 5.57 μg/mL and 1.90± 1.87 μg/mL in plasma, respectively. The mean NVCM levels significantly increased at all time-points in cornea, iris, and ciliary body (p< 0.05) in the CTOIDD group. The AUC0– 24 values in the CTOIDD group were 27,543.70 μg·h/g in cornea, 32,514.48 μg·h/g in conjunctiva, 8631.05 μg·h/g in iris, 2194.36 μg·h/g in ciliary body and 343.9 μg·h/mL in aqueous humour, which were higher than for the eye drop group in all tissues.Conclusion: Since continuous instillation of NVCM with CTOIDD could reach significantly higher concentrations and was sustained for a longer period compared with hourly administration of eye drop, CTOIDD administered NVCM could be a possible method to treat bacterial keratitis.Keywords: topical drug delivery, ocular tissue, anterior segment, area under the curve, rabbit eye |
topic |
topical drug delivery ocular tissue anterior segment area under the curve rabbit eye |
url |
https://www.dovepress.com/comparative-assessment-of-distribution-characteristics-and-ocular-phar-peer-reviewed-article-DDDT |
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