• 1.

    Brooks DE, Matthews AG. Equine ophthalmology. In: Gelatt KN, ed. Veterinary ophthalmology. Ames, Iowa: Blackwell, 2007;11651274.

  • 2.

    Moore CP, Fales WH, Whittington P, et al. Bacterial and fungal isolates from Equidae with ulcerative keratitis. J Am Vet Med Assoc 1983; 182:600603.

    • Search Google Scholar
    • Export Citation
  • 3.

    Keller RL, Hendrix DV. Bacterial isolates and antimicrobial susceptibilities in equine bacterial ulcerative keratitis (1993–2004). Equine Vet J 2005; 37:207211.

    • Search Google Scholar
    • Export Citation
  • 4.

    Sauer P, Andrew SE, Lassaline M, et al. Changes in antibiotic resistance in equine bacterial ulcerative keratitis (1991–2000): 65 horses. Vet Ophthalmol 2003; 6:309313.

    • Search Google Scholar
    • Export Citation
  • 5.

    Chaudhry NA, Flynn HW, Murray TG, et al. Emerging cipro-floxacin-resistant Pseudomonas aeruginosa. Am J Ophthalmol 1999; 128:509510.

  • 6.

    Goldstein MH, Kowalski RP, Gordon YJ. Emerging fluoroquinolone resistance in bacterial keratitis—a 5-year review. Ophthalmology 1999; 106:13131318.

    • Search Google Scholar
    • Export Citation
  • 7.

    Ince D, Hooper DC. Mechanisms and frequency of resistance to gatifloxacin in comparison to AM-1121 and ciprofloxacin in Staphylococcus aureus. Antimicrob Agents Chemother 2001; 45:27552764.

    • Search Google Scholar
    • Export Citation
  • 8.

    Robertson SM, Curtis MA, Schlech BA, et al. Ocular pharmacokinetics of moxifloxacin after topical treatment of animals and humans. Surv Ophthalmol 2005; 50(suppl 1):S32S45.

    • Search Google Scholar
    • Export Citation
  • 9.

    Callegan MC, Ramirez R, Kane ST, et al. Antibacterial activity of the fourth-generation fluoroquinolones gatifloxacin and moxifloxacin against ocular pathogens. Adv Ther 2003; 20:246252.

    • Search Google Scholar
    • Export Citation
  • 10.

    Chawla B, Agarwal P, Tandon R, et al. In vitro susceptibility of bacterial keratitis isolates to fourth-generation fluooquinolones. Eur J Ophthalmol 2010; 20:300305.

    • Search Google Scholar
    • Export Citation
  • 11.

    Duggirala A, Joseph J, Sharma S, et al. Activity of newer fluoroquinolones against gram-positive and gram-negative bacteria isolated from ocular infections: an in vitro comparison. Indian J Ophthalmol 2007; 55:1519.

    • Search Google Scholar
    • Export Citation
  • 12.

    Cekic O, Batman C, Totan Y, et al. Penetration of ofloxacin and ciprofloxacin in aqueous humor after topical administration. Ophthalmic Surg Lasers 1999; 30:465468.

    • Search Google Scholar
    • Export Citation
  • 13.

    Diamond JP, White L, Leeming JP, et al. 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; 79:606609.

    • Search Google Scholar
    • Export Citation
  • 14.

    Healy DP, Holland EJ, Nordlund ML, et al. Concentrations of levofloxacin, ofloxacin, and ciprofloxacin in human corneal stromal tissue and aqueous humor after topical administration. Cornea 2004; 23:255263.

    • Search Google Scholar
    • Export Citation
  • 15.

    McDermott ML, Tran TD, Cowden JW, et al. Corneal stromal penetration of topical ciprofloxacin in humans. Ophthalmology 1993; 100:197200.

  • 16.

    Hendrix DV, Stuffle JL, Cox SK. Pharmacokinetics of topically applied ciprofloxacin in equine tears. Vet Ophthalmol 2007; 10:344347.

  • 17.

    Limberg M, Bugge C. Tear concentrations of topically applied ciprofloxacin. Cornea 1994; 13:496499.

  • 18.

    Green LC, Callegan MC, Engel LS, et al. Pharmacokinetics of topically applied ciprofloxacin in rabbit tears. Jpn J Ophthalmol 1996; 40:123126.

    • Search Google Scholar
    • Export Citation
  • 19.

    Richman J, Zolezio H, Tang-Liu D. Comparison of ofloxacin. gentamicin, and tobramycin concentrations in tears and in vitro MICs for 90% of test organisms. Antimicrob Agents Chemother 1990; 34:16021604.

    • Search Google Scholar
    • Export Citation
  • 20.

    Raizman MB, Rubin JM, Graves AL, et al. Tear concentrations of levofloxacin following topical administration of a single dose of 0.5% levofloxacin ophthalmic solution in healthy volunteers. Clin Ther 2002; 24:14391450.

    • Search Google Scholar
    • Export Citation
  • 21.

    Akkan AG, Mutlu I, Ozyazgan S, et al. Comparative tear concentrations of topically applied ciprofloxacin, ofloxacin, and norfloxacin in human eyes. Int J Clin Pharmacol Ther 1997; 35:214217.

    • Search Google Scholar
    • Export Citation
  • 22.

    Prescott JF, Yielding KM. In vitro susceptibility of selected veterinary bacterial pathogens to ciprofloxacin, enrofloxacin, and norfloxacin. Can J Vet Res 1990; 54:195197.

    • Search Google Scholar
    • Export Citation
  • 23.

    Kowalski RP, Yates KA, Romanowski EG, et al. An ophthalmologist's guide to understanding antibiotic susceptibility and minimum inhibitory concentration data. Ophthalmology 2005; 112:19871991.

    • Search Google Scholar
    • Export Citation
  • 24.

    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; 136:500505.

    • Search Google Scholar
    • Export Citation
  • 25.

    Yalvac IS, Basci NE, Bozkurt A, et al. Penetration of topically applied ciprofloxacin and ofloxacin into the aqueous humor and vitreous. J Cataract Refract Surg 2003; 29:487491.

    • Search Google Scholar
    • Export Citation
  • 26.

    Yu-Speight AW, Kern TJ, Erb HN. Ciprofloxacin and ofloxacin aqueous humor concentrations after topical administration in dogs undergoing cataract surgery. Vet Ophthalmol 2005; 8:181187.

    • Search Google Scholar
    • Export Citation
  • 27.

    DeSantis LM, Patil PN. Pharmacokinetics. In: Mauger TF, Craig EL, eds. Havener's ocular pharmacology. 6th ed. St Louis: Mosby, 1994;37.

  • 28.

    Sosa AB, Epstein SP, Asbell PA. Evaluation of toxicity of commercial ophthalmic fluoroquinolone antibiotics as assessed on immortalized corneal and conjunctival epithelial cells. Cornea 2008; 27:930934.

    • Search Google Scholar
    • Export Citation
  • 29.

    Tsai TH, Chen WL, Hu FR. Comparison of fluoroquinolones: cytotoxicity on human corneal epithelial cells. Eye (Lond) 2010; 24:909917.

  • 30.

    Cha S-H, Lee J-S, Oum B-S, et al. Corneal epithelial cellular dysfunction from benzalkonium chloride (BAC) in vitro. Clin Experiment Ophthalmol 2004; 32:180184.

    • Search Google Scholar
    • Export Citation
  • 31.

    Grant RL, Acosta D. Prolonged adverse effects of benzalkonium chloride and sodium dodecyl sulfate in a primary culture system of rabbit corneal epithelial cells. Fundam Appl Toxicol 1996; 33:7182.

    • Search Google Scholar
    • Export Citation
  • 32.

    Asbell PA, Colby KA, Deng S, et al. Ocular TRUST: nationwide antimicrobial susceptibility patterns in ocular isolates. Am J Ophthalmol 2008; 145:951958.

    • Search Google Scholar
    • Export Citation

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Tear, cornea, and aqueous humor concentrations of ciprofloxacin and moxifloxacin after topical ocular application in ophthalmologically normal horses

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  • 1 Veterinary Teaching Hospital, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.
  • | 2 Veterinary Teaching Hospital, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.
  • | 3 Veterinary Teaching Hospital, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.
  • | 4 Veterinary Teaching Hospital, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996.

Abstract

Objective—To determine ocular tissue drug concentrations after topical ocular administration of 0.3% ciprofloxacin and 0.5% moxifloxacin in ophthalmologically normal horses.

Animals—24 ophthalmologically normal adult horses.

Procedures—0.3% ciprofloxacin and 0.5% moxifloxacin solutions (0.1 mL) were applied to the ventral conjunctival fornix of 1 eye in each horse as follows: group 1 (n = 8) at 0, 2, 4, and 6 hours; group 2 (8) at 0, 2, 4, 6, and 10 hours; and group 3 (8) at 0, 2, 4, 6, 10, and 14 hours. Tears, cornea, and aqueous humor (AH) were collected at 8, 14, and 18 hours for groups 1, 2, and 3, respectively. Drug concentrations were determined via high-performance liquid chromatography.

Results—Median (25th to 75th percentile) concentrations of ciprofloxacin for groups 1, 2, and 3 in tears (μg/mL) were 53.7 (25.5 to 88.8), 48.5 (19.7 to 74.7), and 24.4 (15.4 to 67.1), respectively; in corneal tissue (μg/g) were 0.95 (0.60 to 1.02), 0.37 (0.32 to 0.47), and 0.48 (0.34 to 0.95), respectively; and in AH were lower than the limit of quantification in all groups. Concentrations of moxifloxacin for groups 1, 2, and 3 in tears (μg/mL) were 188.7 (44.5 to 669.2), 107.4 (41.7 to 296.5), and 178.1 (70.1 to 400.6), respectively; in corneal tissue (μg/g) were 1.84 (1.44 to 2.11), 0.78 (0.55 to 0.98), and 0.77 (0.65 to 0.97), respectively; and in AH (μg/mL) were 0.06 (0.04 to 0.08), 0.03 (0.02 to 0.05), and 0.02 (0.01 to 0.04), respectively. Corneal moxifloxacin concentrations were significantly higher in group 1 than groups 2 and 3.

Conclusions and Clinical Relevance—After topical ocular administration, fluoroquinolones can reach therapeutic concentrations in tears and corneal tissue of horses, even when there is an intact epithelium.

Abstract

Objective—To determine ocular tissue drug concentrations after topical ocular administration of 0.3% ciprofloxacin and 0.5% moxifloxacin in ophthalmologically normal horses.

Animals—24 ophthalmologically normal adult horses.

Procedures—0.3% ciprofloxacin and 0.5% moxifloxacin solutions (0.1 mL) were applied to the ventral conjunctival fornix of 1 eye in each horse as follows: group 1 (n = 8) at 0, 2, 4, and 6 hours; group 2 (8) at 0, 2, 4, 6, and 10 hours; and group 3 (8) at 0, 2, 4, 6, 10, and 14 hours. Tears, cornea, and aqueous humor (AH) were collected at 8, 14, and 18 hours for groups 1, 2, and 3, respectively. Drug concentrations were determined via high-performance liquid chromatography.

Results—Median (25th to 75th percentile) concentrations of ciprofloxacin for groups 1, 2, and 3 in tears (μg/mL) were 53.7 (25.5 to 88.8), 48.5 (19.7 to 74.7), and 24.4 (15.4 to 67.1), respectively; in corneal tissue (μg/g) were 0.95 (0.60 to 1.02), 0.37 (0.32 to 0.47), and 0.48 (0.34 to 0.95), respectively; and in AH were lower than the limit of quantification in all groups. Concentrations of moxifloxacin for groups 1, 2, and 3 in tears (μg/mL) were 188.7 (44.5 to 669.2), 107.4 (41.7 to 296.5), and 178.1 (70.1 to 400.6), respectively; in corneal tissue (μg/g) were 1.84 (1.44 to 2.11), 0.78 (0.55 to 0.98), and 0.77 (0.65 to 0.97), respectively; and in AH (μg/mL) were 0.06 (0.04 to 0.08), 0.03 (0.02 to 0.05), and 0.02 (0.01 to 0.04), respectively. Corneal moxifloxacin concentrations were significantly higher in group 1 than groups 2 and 3.

Conclusions and Clinical Relevance—After topical ocular administration, fluoroquinolones can reach therapeutic concentrations in tears and corneal tissue of horses, even when there is an intact epithelium.

Contributor Notes

Dr. Westermeyer's present address is Peace Avenue Veterinary Clinic, 7B Liberty Ave, MongKok, China.

Supported by the American College of Veterinary Ophthalmologists Vision for Animals Foundation and the Department of Small Animal Clinical Sciences, University of Tennessee.

Presented in abstract form at the Annual Conference of the American College of Veterinary Ophthalmologists, Chicago, November 2009.

Address correspondence to Dr. Hendrix (dhendrix@utk.edu).