Fourth-Generation Fluoroquinolone Penetration into the Aqueous Humor in Humans

James P McCulley, D. Caudle, J. D. Aronowicz, W. E. Shine

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Purpose: To compare the penetration and levels of the fourth-generation fluoroquinolones moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% solution in the aqueous humor (AH) in humans after topical application with published levels of other available fluoroquinolones under similar dosing conditions. Design: Prospective, randomized, double-masked clinical trial. Participants: Forty-six patients undergoing cataract extraction. Methods: Patients scheduled for routine phacoemulsification and intraocular lens implantation were provided either moxifloxacin 0.5% ophthalmic solution (n = 22) or gatifloxacin 0.3% ophthalmic solution (n = 24) to use 4 times daily the day before surgery plus 1 drop 1 hour before the surgical entry into the anterior chamber on the day of surgery. This regimen simulated a realistic postoperative dosing schedule. Aqueous humor samples were obtained and analyzed by high-pressure liquid chromatography. Aqueous humor fluoroquinolone concentrations were calculated by peak comparison with a known concentration peak for ciprofloxacin that was used as an internal standard. These values were compared with published concentrations of other available fluoroquinolones under similar dosing conditions. Results: The mean age of the moxifloxacin 0.5% group was 67.8±9.7 years, whereas that of the gatifloxacin 0.3% group was 69.9±8.7 years. The moxifloxacin AH concentration was 1.86±1.06 μg/ml, and that of gatifloxacin was 0.94±0.72 μg/ml. This 2-fold difference was statistically significant (P = 0.001). Conclusions: Aqueous humor antibiotic concentrations achieved at the time of cataract surgery after topical application can serve as an effective surrogate for what can be achieved with typical postoperative topical dosing (e.g., 4 times daily). Both fourth-generation fluoroquinolones achieved a greater AH concentration after 4 times daily dosing relative to prior-generation fluoroquinolones. Moxifloxacin 0.5% ophthalmic solution achieved a 2-fold higher aqueous humor concentration than gatifloxacin 0.3% ophthalmic solution. The superior penetration of moxifloxacin into the AH may be attributed partially to its high degree of lipophilicity, greater solubility at neutral pH, and higher concentration in the commercial formulation. The enhanced penetration of moxifloxacin 0.5% ophthalmic solution may provide better protection against ocular infections.

Original languageEnglish (US)
Pages (from-to)955-959
Number of pages5
JournalOphthalmology
Volume113
Issue number6
DOIs
StatePublished - Jun 2006

Fingerprint

Aqueous Humor
Fluoroquinolones
Ophthalmic Solutions
Ambulatory Surgical Procedures
Eye Infections
Intraocular Lens Implantation
Phacoemulsification
Cataract Extraction
Anterior Chamber
Ciprofloxacin
moxifloxacin
Solubility
Cataract
Appointments and Schedules
High Pressure Liquid Chromatography
gatifloxacin
Clinical Trials
Anti-Bacterial Agents

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Fourth-Generation Fluoroquinolone Penetration into the Aqueous Humor in Humans. / McCulley, James P; Caudle, D.; Aronowicz, J. D.; Shine, W. E.

In: Ophthalmology, Vol. 113, No. 6, 06.2006, p. 955-959.

Research output: Contribution to journalArticle

McCulley, James P ; Caudle, D. ; Aronowicz, J. D. ; Shine, W. E. / Fourth-Generation Fluoroquinolone Penetration into the Aqueous Humor in Humans. In: Ophthalmology. 2006 ; Vol. 113, No. 6. pp. 955-959.
@article{7e4452dd6feb4544b8e01a353d5b4e74,
title = "Fourth-Generation Fluoroquinolone Penetration into the Aqueous Humor in Humans",
abstract = "Purpose: To compare the penetration and levels of the fourth-generation fluoroquinolones moxifloxacin 0.5{\%} ophthalmic solution and gatifloxacin 0.3{\%} solution in the aqueous humor (AH) in humans after topical application with published levels of other available fluoroquinolones under similar dosing conditions. Design: Prospective, randomized, double-masked clinical trial. Participants: Forty-six patients undergoing cataract extraction. Methods: Patients scheduled for routine phacoemulsification and intraocular lens implantation were provided either moxifloxacin 0.5{\%} ophthalmic solution (n = 22) or gatifloxacin 0.3{\%} ophthalmic solution (n = 24) to use 4 times daily the day before surgery plus 1 drop 1 hour before the surgical entry into the anterior chamber on the day of surgery. This regimen simulated a realistic postoperative dosing schedule. Aqueous humor samples were obtained and analyzed by high-pressure liquid chromatography. Aqueous humor fluoroquinolone concentrations were calculated by peak comparison with a known concentration peak for ciprofloxacin that was used as an internal standard. These values were compared with published concentrations of other available fluoroquinolones under similar dosing conditions. Results: The mean age of the moxifloxacin 0.5{\%} group was 67.8±9.7 years, whereas that of the gatifloxacin 0.3{\%} group was 69.9±8.7 years. The moxifloxacin AH concentration was 1.86±1.06 μg/ml, and that of gatifloxacin was 0.94±0.72 μg/ml. This 2-fold difference was statistically significant (P = 0.001). Conclusions: Aqueous humor antibiotic concentrations achieved at the time of cataract surgery after topical application can serve as an effective surrogate for what can be achieved with typical postoperative topical dosing (e.g., 4 times daily). Both fourth-generation fluoroquinolones achieved a greater AH concentration after 4 times daily dosing relative to prior-generation fluoroquinolones. Moxifloxacin 0.5{\%} ophthalmic solution achieved a 2-fold higher aqueous humor concentration than gatifloxacin 0.3{\%} ophthalmic solution. The superior penetration of moxifloxacin into the AH may be attributed partially to its high degree of lipophilicity, greater solubility at neutral pH, and higher concentration in the commercial formulation. The enhanced penetration of moxifloxacin 0.5{\%} ophthalmic solution may provide better protection against ocular infections.",
author = "McCulley, {James P} and D. Caudle and Aronowicz, {J. D.} and Shine, {W. E.}",
year = "2006",
month = "6",
doi = "10.1016/j.ophtha.2006.01.061",
language = "English (US)",
volume = "113",
pages = "955--959",
journal = "Ophthalmology",
issn = "0161-6420",
publisher = "Elsevier Inc.",
number = "6",

}

TY - JOUR

T1 - Fourth-Generation Fluoroquinolone Penetration into the Aqueous Humor in Humans

AU - McCulley, James P

AU - Caudle, D.

AU - Aronowicz, J. D.

AU - Shine, W. E.

PY - 2006/6

Y1 - 2006/6

N2 - Purpose: To compare the penetration and levels of the fourth-generation fluoroquinolones moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% solution in the aqueous humor (AH) in humans after topical application with published levels of other available fluoroquinolones under similar dosing conditions. Design: Prospective, randomized, double-masked clinical trial. Participants: Forty-six patients undergoing cataract extraction. Methods: Patients scheduled for routine phacoemulsification and intraocular lens implantation were provided either moxifloxacin 0.5% ophthalmic solution (n = 22) or gatifloxacin 0.3% ophthalmic solution (n = 24) to use 4 times daily the day before surgery plus 1 drop 1 hour before the surgical entry into the anterior chamber on the day of surgery. This regimen simulated a realistic postoperative dosing schedule. Aqueous humor samples were obtained and analyzed by high-pressure liquid chromatography. Aqueous humor fluoroquinolone concentrations were calculated by peak comparison with a known concentration peak for ciprofloxacin that was used as an internal standard. These values were compared with published concentrations of other available fluoroquinolones under similar dosing conditions. Results: The mean age of the moxifloxacin 0.5% group was 67.8±9.7 years, whereas that of the gatifloxacin 0.3% group was 69.9±8.7 years. The moxifloxacin AH concentration was 1.86±1.06 μg/ml, and that of gatifloxacin was 0.94±0.72 μg/ml. This 2-fold difference was statistically significant (P = 0.001). Conclusions: Aqueous humor antibiotic concentrations achieved at the time of cataract surgery after topical application can serve as an effective surrogate for what can be achieved with typical postoperative topical dosing (e.g., 4 times daily). Both fourth-generation fluoroquinolones achieved a greater AH concentration after 4 times daily dosing relative to prior-generation fluoroquinolones. Moxifloxacin 0.5% ophthalmic solution achieved a 2-fold higher aqueous humor concentration than gatifloxacin 0.3% ophthalmic solution. The superior penetration of moxifloxacin into the AH may be attributed partially to its high degree of lipophilicity, greater solubility at neutral pH, and higher concentration in the commercial formulation. The enhanced penetration of moxifloxacin 0.5% ophthalmic solution may provide better protection against ocular infections.

AB - Purpose: To compare the penetration and levels of the fourth-generation fluoroquinolones moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% solution in the aqueous humor (AH) in humans after topical application with published levels of other available fluoroquinolones under similar dosing conditions. Design: Prospective, randomized, double-masked clinical trial. Participants: Forty-six patients undergoing cataract extraction. Methods: Patients scheduled for routine phacoemulsification and intraocular lens implantation were provided either moxifloxacin 0.5% ophthalmic solution (n = 22) or gatifloxacin 0.3% ophthalmic solution (n = 24) to use 4 times daily the day before surgery plus 1 drop 1 hour before the surgical entry into the anterior chamber on the day of surgery. This regimen simulated a realistic postoperative dosing schedule. Aqueous humor samples were obtained and analyzed by high-pressure liquid chromatography. Aqueous humor fluoroquinolone concentrations were calculated by peak comparison with a known concentration peak for ciprofloxacin that was used as an internal standard. These values were compared with published concentrations of other available fluoroquinolones under similar dosing conditions. Results: The mean age of the moxifloxacin 0.5% group was 67.8±9.7 years, whereas that of the gatifloxacin 0.3% group was 69.9±8.7 years. The moxifloxacin AH concentration was 1.86±1.06 μg/ml, and that of gatifloxacin was 0.94±0.72 μg/ml. This 2-fold difference was statistically significant (P = 0.001). Conclusions: Aqueous humor antibiotic concentrations achieved at the time of cataract surgery after topical application can serve as an effective surrogate for what can be achieved with typical postoperative topical dosing (e.g., 4 times daily). Both fourth-generation fluoroquinolones achieved a greater AH concentration after 4 times daily dosing relative to prior-generation fluoroquinolones. Moxifloxacin 0.5% ophthalmic solution achieved a 2-fold higher aqueous humor concentration than gatifloxacin 0.3% ophthalmic solution. The superior penetration of moxifloxacin into the AH may be attributed partially to its high degree of lipophilicity, greater solubility at neutral pH, and higher concentration in the commercial formulation. The enhanced penetration of moxifloxacin 0.5% ophthalmic solution may provide better protection against ocular infections.

UR - http://www.scopus.com/inward/record.url?scp=33646925640&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33646925640&partnerID=8YFLogxK

U2 - 10.1016/j.ophtha.2006.01.061

DO - 10.1016/j.ophtha.2006.01.061

M3 - Article

C2 - 16603244

AN - SCOPUS:33646925640

VL - 113

SP - 955

EP - 959

JO - Ophthalmology

JF - Ophthalmology

SN - 0161-6420

IS - 6

ER -