Abstract
Introduction
Achieving high antibiotic concentrations is important for preventing and treating postoperative infections. However, no study has simultaneously compared the achieved concentrations of moxifloxacin, gatifloxacin, and levofloxacin in the human cornea and aqueous humor. The authors therefore performed a randomized study to determine the concentrations of 0.5% moxifloxacin, 0.3% gatifloxacin, and 0.5% levofloxacin in the corneal tissue and aqueous humor after topical instillation in patients undergoing penetrating keratoplasty.
Methods
Patients who required penetrating keratoplasty were eligible for this study. The topical preparations of 0.5% moxifloxacin, 0.3% gatifloxacin, and 0.5% levofloxacin used in the study were preservative free (Japanese formulations). Patients were randomly assigned to one of three sequential drug groups, in which each drug was administered three times before surgery. In each administration cycle, the patients received two drops of each drug at 2-minute intervals. Samples of corneal tissue and aqueous humor were collected during surgery. The concentrations of each drug in the samples were determined by high-performance liquid chromatography.
Results
A total of 63 patients across eight centers in Japan were enrolled in the study. Overall, 61 corneal and 58 aqueous humor samples were evaluated. The concentration (mean ± standard deviation) of moxifloxacin in corneal tissues was 12.66 ± 8.93 μg/g, which was significantly higher than that of gatifloxacin (4.71 ± 3.39 μg/g; P < 0.0001) and levofloxacin (5.95 ± 4.02 μg/g; P < 0.0001). The mean concentration of moxifloxacin in aqueous humor samples was 1.40 ± 1.17 μg/mL, which was significantly higher than that of gatifloxacin (0.65 ± 0.80 μg/mL; P = 0.0001) and levofloxacin (0.89 ± 0.86 μg/mL; P < 0.05). The sequence of drug administration did not significantly affect the results.
Conclusion
These results show that 0.5% moxifloxacin achieved superior ocular concentration than both 0.3% gatifloxacin and 0.5% levofloxacin.
Similar content being viewed by others
References
Miller JJ, Scott IU, Flynn HW Jr, Smiddy WE, Newton J, Miller D. Acute-onset endophthalmitis after cataract surgery (2000–2004): incidence, clinical settings, and visual acuity outcomes after treatment. Am J Ophthalmol. 2005;139:983–98
Kowalski RP, Dhaliwal DK, Karenchak LM, et al. Gatifloxacin and moxifloxacin: an in vitro susceptibility comparison to levofloxacin, ciprofloxacin, and ofloxacin using bacterial keratitis isolates. Am J Ophthalmol. 2003;136:500–505.
Mather R, Karenchak LM, Romanowski EG, Kowalski RP. Fourth generation fluoroquinolones: new weapons in the arsenal of ophthalmic antibiotics. Am J Ophthalmol. 2002;133:463–466.
Scoper SV. Review of third-and fourth-generation fluoroquinolones in ophthalmology: in-vitro and in-vivo efficacy. Adv Ther. 2008;25:979–994.
Mauger TF. Antimicrobials. In: Mauger TF, Craig EL, eds. Havener’s Ocular Pharmacology. 6th edition. St. Louis: Mosby; 1994:234–349.
Fukuda M, Sasaki H. Calculation of AQCmax: comparison of five ophthalmic fluoroquinolone solutions. Curr Med Res Opin. 2008;24:3479–3485.
Sugioka K, Fukuda M, Komoto S, Itahashi M, Yamada M, Shimomura Y. Intraocular penetration of sequentially instilled topical moxifloxacin, gatifloxacin, and levofloxacin. Clin Ophthalmol. 2009;3:553–557.
Kim DH, Stark WJ, O’Brien TP, Dick JD. Aqueous penetration and biological activity of moxifloxacin 0.5% ophthalmic solution and gatifloxacin 0.3% solution in cataract surgery patients. Ophthalmology. 2005;112:1992–1996.
McCulley JP, Caudle D, Aronowicz JD, Sine WE. Fourth-generation fluoroquinolone penetration into the aqueous humor in humans. Ophthalmology. 2006;113:955–959.
Holland EJ, Lane SS, Kim T, Raizman M, Dunn S. Ocular penetration and pharmacokinetics of topical gatifloxacin 0.3% and moxifloxacin 0.5% ophthalmic solutions after keratoplasty. Cornea. 2008;27:314–319.
Owen GR, Brooks AC, James O, Robertson SM. A novel in vivo rabbit model that mimics human dosing to determine the distribution of antibiotics in ocular tissues. J Ocul Pharmacol Ther. 2007;23:335–342.
Yamada M, Mochizuki H, Yamada K, Kawai M, Mashima Y. Aqueous humor levels of topically applied levofloxacin, norfloxacin, and lomefloxacin in the same human eyes. J Cataract Refract Surg. 2003;29:1771–1775.
Yamada M, Ishikawa K, Mochizuki H, Kawai M. Corneal penetration of simultaneously applied topical levofloxacin, norfloxacin and lomefloxacin in human eyes. Acta Ophthalmol Scand. 2006;84:192–196.
Liesegang TJ. Use of antimicrobials to prevent postoperative infection in patients with cataracts. Curr Opin Ophthalmol. 2001;12:68–74.
Katz HR, Masket S, Lane SS, et al. Absorption of topical moxifloxacin ophthalmic solution into human aqueous humor. Cornea. 2005:24:955–958.
Robertson SM, Curtis MA, Schlech BA, et al. Ocular pharmacokinetics of moxifloxacin after topical treatment of animals and humans. Surv Ophthalmol. 2005;50:S32–S45.
Baudouin C. Detrimental effect of preservatives in eyedrops: implications for the treatment of glaucoma. Acta Ophthalmol. 2003;136:76–81.
Hyon JY, Eser I, O’Brien TP. Kill rates of preserved and preservative-free topical 8-methoxy fluoroquinolones against various strains of Staphylococcus. J Cataract Refract Surg. 2009;35:1609–1613
Donnenfeld ED, Perry HD, Snyder RW, Moadel R, Elsky M, Jones H. Intracorneal, aqueous humor, and vitreous humor penetration of topical and oral ofloxacin. Arch Ophthalmol. 1997;115:173–176.
Price FW Jr, Whitson WE, Gonzales J, Johns S. Corneal tissue levels of topically applied ofloxacin. J Cataract Refract Surg. 1997;23:898–902.
Diamond JP, White L, Leeming JP, Bing Hoh H, Easty DL. Topical 0.3% ciprofloxacin, norfloxacin, and ofloxacin in treatment of bacterial keratitis: a new method for comparative evaluation of ocular drug penetration. Br J Ophthalmol. 1995;79:606–609.
DeSantis LM. Pharmacokinetics. In: Mauger TF, Craig EL, eds. Havener’s Ocular Pharmacology. 6th edition. St. Louis: Mosby; 1994:22–52.
Colleaux KM, Hamilton WK. Effect of prophylactic antibiotics and incision type on the incidence of endophthalmitis after cataract surgery. Can J Ophthalmol. 2000;35:373–378.
Brown L. Resistance to ocular antibiotics: an overview. Clin Exp Optom. 2007;90:258–262.
Hwang DG. Fluoroquinolone resistance in ophthalmology and the potential role for newer ophthalmic fluoroquinolones. Surv Ophthalmol. 2004;49:S79–S83.
Alexandrakis G, Alfonso EC, Miller D. Shifting trends in bacterial keratitis in south Florida and emerging resistance to fluoroquinolones. Ophthalmology. 2000;107:1497–1502.
Goldstein MH, Kowalski RP, Gordon YJ. Emerging fluoroquinolone resistance in bacterial keratitis: a 5-year review. Ophthalmology. 1999;106: 1313–1318.
Firsov AA, Vostrov SN, Lubenko IY, Drlica K, Portnoy YA, Zinner SH. In vitro pharmacodynamic evaluation of the mutant selection window hypothesis using four fluoroquinolones against Staphylococcus aureus. Antimicrob Agents Chemother. 2003;47:1604–1613.
Zhao X, Drlica K. Restricting the selection of antibiotic-resistant mutant bacteria: measurement and potential use of the mutant selection window. J Infect Dis. 2002;185:561–565.
Kim DH, Stark WJ, O’Brien TP. Ocular penetration of moxifloxacin 0.5% and gatifloxacin 0.3% ophthalmic solutions into the aqueous humor following topical administration prior to routine cataract surgery. Curr Med Res Opin. 2005;21:93–94.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Fukuda, M., Yamada, M., Kinoshita, S. et al. Comparison of Corneal and Aqueous Humor Penetration of Moxifloxacin, Gatifloxacin and Levofloxacin during Keratoplasty. Adv Therapy 29, 339–349 (2012). https://doi.org/10.1007/s12325-012-0016-x
Received:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12325-012-0016-x