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Evaluation of Moxifloxacin, Ciprofloxacin, Gatifloxacin, Ofloxacin, and Levofloxacin Concentrations in Human Conjunctival Tissue

Evaluation of Moxifloxacin, Ciprofloxacin, Gatifloxacin, Ofloxacin, and Levofloxacin... The efficacy of a topical ocular antibiotic relies primarily on its structure, its mechanism of action, and its penetration to the intended site of action. Rapid penetration into the target tissue can translate to greater efficacy and more expedient elimination of bacteria. Effective penetration of medication can therefore have a depot effect and aid in minimizing the spread of infection and reducing the likelihood of bacterial development of resistance. Clinicians must recognize the importance of tissue-concentration data and the fact that gathering them requires conjunctival biopsy to assess the relative abilities of ophthalmic agents to maintain effective concentrations in the conjunctiva. This study presents a new dual-biopsy technique that has the potential to become a universally approved, standardized means of evaluating topical ocular antibiotics. The purpose of this study was to determine the concentrations of 0.5% moxifloxacin (Vigamox; Alcon Laboratories Inc, Fort Worth, Tex), 0.3% ciprofloxacin (Ciloxan; Alcon Laboratories Inc), 0.3% gatifloxacin (Zymar; Allergan Inc, Irvine, Calif), 0.3% ofloxacin (Ocuflox; Allergan Inc), and 0.5% levofloxacin (Quixin; Santen Incorporated, Napa, Calif) ophthalmic solutions in conjunctival tissue following a single dose of study medication 20 minutes after instillation. Methods All human subjects underwent screening and baseline slitlamp examination followed by preparation for biopsy from 1 eye per subject. According to a predetermined randomization scheme, moxifloxacin, ciprofloxacin, gatifloxacin, ofloxacin, or levofloxacin was instilled in the study eye 20 minutes prior to biopsy. Two palpebral conjunctival biopsies were taken from the study eye (1 each from the temporal and nasal regions of the inferior cul-de-sac) and were then shipped to the laboratory for analysis. Prepared samples were analyzed by a dual-analyte, reversed-phase high-pressure liquid chromatography method. Subjects were followed up for 1 week. Results Following a single dose of moxifloxacin (n = 15), ciprofloxacin (n = 12), gatifloxacin (n = 14), ofloxacin (n = 13), or levofloxacin (n = 12), the conjunctival levels of moxifloxacin were statistically significantly higher than those of the other 4 fluoroquinolones (P<.001) (Figure). There was no statistically significant difference between the conjunctival concentrations of the other 4 fluoroquinolones when moxifloxacin was excluded from the analysis (p = .35). View LargeDownload Figure. Conjunctival pharmacokinetics of topical ocular antibiotics 20 minutes after healthy volunteers received a single drop. Statistical comparison across treatments shows a highly significant difference (P<.001) when ciprofloxacin, gatifloxacin, ofloxacin, and levofloxacin are compared with moxifloxacin. When the analysis is repeated excluding moxifloxacin, the statistical difference disappears (P = .35), indicating that these 4 fluoroquinolones are not significantly different from one another. Asterisk indicates P<.001. The mean conjunctival concentration of moxifloxacin (18.0 μg/g) was 6.8-fold higher than was observed for ciprofloxacin (2.65 μg/g), 7.1-fold higher than was observed for gatifloxacin (2.54 μg/g), 14.6-fold higher than was observed for ofloxacin (1.23 μg/g), and 7.7-fold higher than was observed for levofloxacin (2.34 μg/g). Conclusion Prior research on the physiochemical characteristics of moxifloxacin has demonstrated that the penetration of moxifloxacin is a result of the molecule’s inherent characteristics. One study has indicated that moxifloxacin exhibits biphasic solubility (both lipophilicity and aqueous solubility) when compared to other fluoroquinolones, including ciprofloxacin, ofloxacin, levofloxacin, and gatifloxacin.1 Additional research using corneal perfusion models has established that the corneal penetration coefficient of moxifloxacin is 3.6 times greater than that of gatifloxacin.2 In this study, significantly greater target tissue penetration was evident with moxifloxacin than with the other 4 fluoroquinolones. Moxifloxacin is a potent antibiotic against the pathogens causing conjunctivitis and is a superior treatment option when penetration of therapeutic concentrations to the conjunctiva is necessary. Correspondence: Dr Abelson, Ophthalmic Research Associates, 863 Turnpike St, North Andover, MA 01845 (aplumer@oraclinical.com). Funding/Support: This study was funded by an educational grant from Alcon Laboratories, Inc (Fort Worth, Tex). References 1. Rusinko AMay JLiao JNamil AHellberg M A study of the enhanced corneal penetration of moxifloxacin. Poster presented at: Association for Research in Vision and Ophthalmology. April 29, 2004 Fort Lauderdale, Fla 2. Owen GRDembinska OStout KRMendiola MK Corneal penetration and changes in corneal permeability of moxifloxacin versus gatifloxacin. Poster presented at: Association for Research in Vision and Ophthalmology. April 29, 2004 Fort Lauderdale, Fla http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Ophthalmology American Medical Association

Evaluation of Moxifloxacin, Ciprofloxacin, Gatifloxacin, Ofloxacin, and Levofloxacin Concentrations in Human Conjunctival Tissue

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Publisher
American Medical Association
Copyright
Copyright © 2005 American Medical Association. All Rights Reserved.
ISSN
0003-9950
eISSN
1538-3687
DOI
10.1001/archopht.123.9.1282
Publisher site
See Article on Publisher Site

Abstract

The efficacy of a topical ocular antibiotic relies primarily on its structure, its mechanism of action, and its penetration to the intended site of action. Rapid penetration into the target tissue can translate to greater efficacy and more expedient elimination of bacteria. Effective penetration of medication can therefore have a depot effect and aid in minimizing the spread of infection and reducing the likelihood of bacterial development of resistance. Clinicians must recognize the importance of tissue-concentration data and the fact that gathering them requires conjunctival biopsy to assess the relative abilities of ophthalmic agents to maintain effective concentrations in the conjunctiva. This study presents a new dual-biopsy technique that has the potential to become a universally approved, standardized means of evaluating topical ocular antibiotics. The purpose of this study was to determine the concentrations of 0.5% moxifloxacin (Vigamox; Alcon Laboratories Inc, Fort Worth, Tex), 0.3% ciprofloxacin (Ciloxan; Alcon Laboratories Inc), 0.3% gatifloxacin (Zymar; Allergan Inc, Irvine, Calif), 0.3% ofloxacin (Ocuflox; Allergan Inc), and 0.5% levofloxacin (Quixin; Santen Incorporated, Napa, Calif) ophthalmic solutions in conjunctival tissue following a single dose of study medication 20 minutes after instillation. Methods All human subjects underwent screening and baseline slitlamp examination followed by preparation for biopsy from 1 eye per subject. According to a predetermined randomization scheme, moxifloxacin, ciprofloxacin, gatifloxacin, ofloxacin, or levofloxacin was instilled in the study eye 20 minutes prior to biopsy. Two palpebral conjunctival biopsies were taken from the study eye (1 each from the temporal and nasal regions of the inferior cul-de-sac) and were then shipped to the laboratory for analysis. Prepared samples were analyzed by a dual-analyte, reversed-phase high-pressure liquid chromatography method. Subjects were followed up for 1 week. Results Following a single dose of moxifloxacin (n = 15), ciprofloxacin (n = 12), gatifloxacin (n = 14), ofloxacin (n = 13), or levofloxacin (n = 12), the conjunctival levels of moxifloxacin were statistically significantly higher than those of the other 4 fluoroquinolones (P<.001) (Figure). There was no statistically significant difference between the conjunctival concentrations of the other 4 fluoroquinolones when moxifloxacin was excluded from the analysis (p = .35). View LargeDownload Figure. Conjunctival pharmacokinetics of topical ocular antibiotics 20 minutes after healthy volunteers received a single drop. Statistical comparison across treatments shows a highly significant difference (P<.001) when ciprofloxacin, gatifloxacin, ofloxacin, and levofloxacin are compared with moxifloxacin. When the analysis is repeated excluding moxifloxacin, the statistical difference disappears (P = .35), indicating that these 4 fluoroquinolones are not significantly different from one another. Asterisk indicates P<.001. The mean conjunctival concentration of moxifloxacin (18.0 μg/g) was 6.8-fold higher than was observed for ciprofloxacin (2.65 μg/g), 7.1-fold higher than was observed for gatifloxacin (2.54 μg/g), 14.6-fold higher than was observed for ofloxacin (1.23 μg/g), and 7.7-fold higher than was observed for levofloxacin (2.34 μg/g). Conclusion Prior research on the physiochemical characteristics of moxifloxacin has demonstrated that the penetration of moxifloxacin is a result of the molecule’s inherent characteristics. One study has indicated that moxifloxacin exhibits biphasic solubility (both lipophilicity and aqueous solubility) when compared to other fluoroquinolones, including ciprofloxacin, ofloxacin, levofloxacin, and gatifloxacin.1 Additional research using corneal perfusion models has established that the corneal penetration coefficient of moxifloxacin is 3.6 times greater than that of gatifloxacin.2 In this study, significantly greater target tissue penetration was evident with moxifloxacin than with the other 4 fluoroquinolones. Moxifloxacin is a potent antibiotic against the pathogens causing conjunctivitis and is a superior treatment option when penetration of therapeutic concentrations to the conjunctiva is necessary. Correspondence: Dr Abelson, Ophthalmic Research Associates, 863 Turnpike St, North Andover, MA 01845 (aplumer@oraclinical.com). Funding/Support: This study was funded by an educational grant from Alcon Laboratories, Inc (Fort Worth, Tex). References 1. Rusinko AMay JLiao JNamil AHellberg M A study of the enhanced corneal penetration of moxifloxacin. Poster presented at: Association for Research in Vision and Ophthalmology. April 29, 2004 Fort Lauderdale, Fla 2. Owen GRDembinska OStout KRMendiola MK Corneal penetration and changes in corneal permeability of moxifloxacin versus gatifloxacin. Poster presented at: Association for Research in Vision and Ophthalmology. April 29, 2004 Fort Lauderdale, Fla

Journal

Archives of OphthalmologyAmerican Medical Association

Published: Sep 1, 2005

Keywords: ciprofloxacin,ofloxacin,conjunctiva,levofloxacin,gatifloxacin,moxifloxacin

References