• 1. Plumb D. Plumb's veterinary drug handbook. 7th ed. Ames, Iowa: Wiley-Blackwell, 2011;362366.

  • 2. Ledbetter E, Gilger B. Diseases and surgery of the canine cornea and sclera. In: Gelatt KN, Gilger BC, Kern TJ, eds. Veterinary ophthalmology. 5th ed. Ames, Iowa: Wiley-Backwell, 2013; 9761049.

    • Search Google Scholar
    • Export Citation
  • 3. Hurn S, Mc Cowan C, Turner A. Oral doxycycline, niacinamide and prednisolone used to treat bilateral nodular granulomatous conjunctivitis of the third eyelid in an Australian Kelpie dog. Vet Ophthalmol 2005; 8: 349352.

    • Search Google Scholar
    • Export Citation
  • 4. Chandler HL, Gemensky-Metzler AJ, Bras ID, et al. In vivo effects of adjunctive tetracycline treatment on refractory corneal ulcers in dogs. J Am Vet Med Assoc 2010; 237: 378386.

    • Search Google Scholar
    • Export Citation
  • 5. Wang L, Pan Q, Xue Q, et al. Evaluation of matrix metalloproteinase concentrations in precorneal tear film from dogs with Pseudomonas aeruginosa-associated keratitis. Am J Vet Res 2008; 69: 13411345.

    • Search Google Scholar
    • Export Citation
  • 6. Gelatt KN, Samuelson DA. Recurrent corneal erosions and epithelial dystrophy in the Boxer dog. J Am Anim Hosp Assoc 1982; 18: 453460.

    • Search Google Scholar
    • Export Citation
  • 7. Kirschner SE, Niyo Y, Betts DM. Idiopathic persistent corneal erosions—clinical and pathological findings in 18 dogs. J Am Anim Hosp Assoc 1989; 25: 8490.

    • Search Google Scholar
    • Export Citation
  • 8. Murphy CJ, Marfurt CF, McDermott A, et al. Spontaneous chronic corneal epithelial defects (SCCED) in dogs: clinical features, innervation, and effect of topical SP, with or without IGF-1. Invest Ophthalmol Vis Sci 2001; 42: 22522261.

    • Search Google Scholar
    • Export Citation
  • 9. Bentley E. Spontaneous chronic corneal epithelial defects in dogs: a review. J Am Anim Hosp Assoc 2005; 41: 158165.

  • 10. Stanley RG, Hardman C, Johnson BW. Results of grid keratotomy, superficial keratectomy and debridement for the management of persistent corneal erosions in 92 dogs. Vet Ophthalmol 1998; 1: 233238.

    • Search Google Scholar
    • Export Citation
  • 11. Kirschner SE, Brazzell RK, Stern ME, et al. The use of topical epidermal growth-factor for treatment of nonhealing corneal erosions in dogs. J Am Anim Hosp Assoc 1991; 27: 449452.

    • Search Google Scholar
    • Export Citation
  • 12. Miller WW. Using polysulfated glycosaminoglycan to treat persistent corneal erosions in dogs. Vet Med 1996; 91: 916922.

  • 13. Bentley E, Murphy CJ. Thermal cautery of the cornea for treatment of spontaneous chronic corneal epithelial defects in dogs and horses. J Am Vet Med Assoc 2004; 224: 250253.

    • Search Google Scholar
    • Export Citation
  • 14. Bromberg NM. Cyanoacrylate tissue adhesive for treatment of refractory corneal ulceration. Vet Ophthalmol 2002; 5: 5560.

  • 15. Ollivier FJ, Gilger BC, Barrie KP, et al. Proteinases of the cornea and preocular tear film. Vet Ophthalmol 2007; 10: 199206.

  • 16. Slansky HH, Gnädinger MC, Itoi M, et al. Collagenase in corneal ulcerations. Arch Ophthalmol 1969; 82: 108111.

  • 17. Ollivier FJ, Brooks DE, Kallberg ME, et al. Evaluation of various compounds to inhibit activity of matrix metalloproteinases in the tear film of horses with ulcerative keratitis. Am J Vet Res 2003; 64: 10811087.

    • Search Google Scholar
    • Export Citation
  • 18. Ollivier FJ, Brooks DE, Kallberg ME, et al. Reduction in matrix metalloproteinase activity in the equine tear film during corneal healing. Invest Ophthalmol Vis Sci 2003; 44: 901.

    • Search Google Scholar
    • Export Citation
  • 19. Brooks DE, Ollivier FJ. Matrix metalloproteinase inhibition in corneal ulceration. Vet Clin North Am Small Anim Pract 2004; 34: 611622.

    • Search Google Scholar
    • Export Citation
  • 20. Ralph RA. Tetracyclines and the treatment of corneal stromal ulceration—a review. Cornea 2000; 19: 274277.

  • 21. Baker A, Plummer CE, Szabo NJ, et al. Doxycycline levels in preocular tear film of horses following oral administration. Vet Ophthalmol 2008; 11: 381385.

    • Search Google Scholar
    • Export Citation
  • 22. Perry HD, Hodes LW, Seedor JA, et al. Effect of doxycycline hyclate on corneal epithelial wound-healing in the rabbit alkali-burn model—preliminary-observations. Cornea 1993;12: 379382.

    • Search Google Scholar
    • Export Citation
  • 23. Griffin MO, Fricovsky E, Ceballos G, et al. Tetracyclines: a pleitropic family of compounds with promising therapeutic properties. Review of the literature. Am J Physiol Cell Physiol 2010; 299: C539C548.

    • Search Google Scholar
    • Export Citation
  • 24. Strubbe DT, Brooks DE, Schultz GS, et al. Evaluation of tear film proteinases in horses with ulcerative keratitis. Vet Ophthalmol 2000; 3: 111119.

    • Search Google Scholar
    • Export Citation
  • 25. Ollivier FJ, Brooks DE, Van Setten GB, et al. Profiles of matrix metalloproteinase activity in equine tear fluid during corneal healing in 10 horses with ulcerative keratitis. Vet Ophthalmol 2004; 7: 397405.

    • Search Google Scholar
    • Export Citation
  • 26. Couture S, Doucet M, Moreau M, et al. Topical effect of various agents on gelatinase activity in the tear film of normal dogs. Vet Ophthalmol 2006; 9: 157164.

    • Search Google Scholar
    • Export Citation
  • 27. Hartmann A, Krebber R, Daube G, et al. Pharmacokinetics of pradofloxacin and doxycycline in serum, saliva, and tear fluid of cats after oral administration. J Vet Pharmacol Ther 2008; 31: 8794.

    • Search Google Scholar
    • Export Citation
  • 28. Freeman KS, Thomasy SM, Stanley SD, et al. Population pharmacokinetics of doxycycline in the tears and plasma of northern elephant seals (Mirounga angustirostris) following oral drug administration. J Am Vet Med Assoc 2013; 243: 11701178.

    • Search Google Scholar
    • Export Citation
  • 29. Li DQ, Lokeshwar BL, Solomon A, et al. Regulation of MMP-9 production by human corneal epithelial cells. Exp Eye Res 2001; 73: 449459.

    • Search Google Scholar
    • Export Citation
  • 30. Luo LH, Li DQ, Doshi A, et al. Experimental dry eye stimulates production of inflammatory cytokines and MMP-9 and activates MAPK signaling pathways on the ocular surface. Invest Ophthalmol Vis Sci 2004; 45: 42934301.

    • Search Google Scholar
    • Export Citation
  • 31. Kafarnik C, Fritsche J, Reese S. Corneal innervation in mesocephalic and brachycephalic dogs and cats: assessment using in vivo confocal microscopy. Vet Ophthalmol 2008; 11: 363367.

    • Search Google Scholar
    • Export Citation
  • 32. Gelatt KN, Gilger BC, Kern TJ. Veterinary ophthalmology. Ames, Iowa: Wiley-Blackwell, 2013.

  • 33. Williams DL. Immunopathogenesis of keratoconjunctivitis sicca in the dog. Vet Clin North Am Small Anim Pract 2008; 38: 251268.

  • 34. KuKanich K, KuKanich B. The effect of sucralfate tablets vs. suspension on oral doxycycline absorption in dogs. J Vet Pharmacol Ther 2015; 38: 169173.

    • Search Google Scholar
    • Export Citation
  • 35. Davis JL, Salmon JH, Papich MG. Pharmacokinetics and tissue distribution of doxycycline after oral administration of single and multiple doses in horses. Am J Vet Res 2006; 67: 310316.

    • Search Google Scholar
    • Export Citation
  • 36. Barza M, Brown RB, Shanks C, et al. Relation between lipophilicity and pharmacological behavior of minocycline, doxycycline, tetracycline, and oxytetracycline in dogs. Antimicrob Agents Chemother 1975; 8: 713720.

    • Search Google Scholar
    • Export Citation
  • 37. Wilson RC, Kemp DT, Kitzman JV, et al. Pharmacokinetics of doxycycline in dogs. Can J Vet Res 1988; 52: 1214.

  • 38. Nazir SA, Murphy S, Siatkowski RM, et al. Ocular rosacea in childhood. Am J Ophthalmol 2004; 137: 138144.

  • 39. Federici TJ. The non-antibiotic properties of tetracyclines: clinical potential in ophthalmic disease. Pharmacol Res 2011; 64: 614623.

    • Search Google Scholar
    • Export Citation
  • 40. Tolar EL, Hendrix DV, Rohrbach BW, et al. Evaluation of clinical characteristics and bacterial isolates in dogs with bacterial keratitis: 97 cases (1993–2003). J Am Vet Med Assoc 2006; 228: 8085.

    • Search Google Scholar
    • Export Citation
  • 41. Maaland MG, Papich MG, Turnidge J, et al. Pharmacodynamics of doxycycline and tetracycline against Staphylococcus pseudintermedius: proposal of canine-specific breakpoints for doxycycline. J Clin Microbiol 2013; 51: 35473554.

    • Search Google Scholar
    • Export Citation
  • 42. Chatterjee SK, Bhattacharjee I, Chandra G. In vitro synergistic effect of doxycycline & ofloxacin in combination with ethanolic leaf extract of Vangueria spinosa against four pathogenic bacteria. Indian J Med Res 2009; 130: 475478.

    • Search Google Scholar
    • Export Citation
  • 43. Goldstein EJ, Citron DM, Merriam CV, et al. Ceftaroline versus isolates from animal bite wounds: comparative in vitro activities against 243 isolates, including 156 Pasteurella species isolates. Antimicrob Agents Chemother 2012; 56: 63196323.

    • Search Google Scholar
    • Export Citation

Advertisement

Tear film concentrations of doxycycline following oral administration in ophthalmologically normal dogs

Sean P. Collins DVM, MS1, Amber L. Labelle DVM, MS2, Levent Dirikolu DVM, PhD3, Zhong Li PhD4, Mark A. Mitchell DVM, PhD5, and Ralph E. Hamor DVM, MS6
View More View Less
  • 1 Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL 61801.
  • | 2 Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL 61801.
  • | 3 Department of Comparative Bioscience, College of Veterinary Medicine, University of Illinois, Urbana, IL 61801.
  • | 4 Department of Metabolomics Center, University of Illinois, Urbana, IL 61801.
  • | 5 Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL 61801.
  • | 6 Department of Veterinary Clinical Medicine, University of Illinois, Urbana, IL 61801.

Abstract

OBJECTIVE To determine tear film concentrations of doxycycline in ophthalmologically normal dogs following oral doxycycline administration.

DESIGN Crossover study.

ANIMALS 10 privately owned dolichocephalic or mesaticephalic dogs free of ophthalmic disease.

PROCEDURES Dogs were randomly assigned to receive doxycycline hyclate first at 5 mg/kg (2.3 mg/lb) or 10 mg/kg (4.5 mg/lb), PO, every 12 hours for 5 days, beginning on day 1. Doxycycline was administered 1 hour prior to feeding. Tear samples were collected from days 1 through 10 approximately 3 hours after the morning dose was administered. Following a 3-week washout period, dogs received the alternative dose in the same conditions. Doxycycline concentration in tear samples from 1 eye (same eye used for both sessions) was measured via liquid chromatography–mass spectrometry and compared between the 2 doxycycline doses.

RESULTS Doxycycline was detected in tear samples of all dogs from days 1 through 10 for both doxycycline doses. Median peak doxycycline concentrations for the 5 mg/kg and 10 mg/kg doses were 2.19 ng/mL on day 3 and 4.32 ng/mL on day 4, respectively. Concentrations differed significantly with time, but this difference was not influenced by dose, dose order, or eye. A significant positive correlation was identified between doxycycline concentration and body weight (r = 0.22).

CONCLUSIONS AND CLINICAL RELEVANCE Detectable doxycycline concentrations were achieved in the tear film of ophthalmologically normal dogs following oral administration of doxycycline at 5 or 10 mg/kg, every 12 hours. Dose had no significant effect on tear film concentration of the drug.

Abstract

OBJECTIVE To determine tear film concentrations of doxycycline in ophthalmologically normal dogs following oral doxycycline administration.

DESIGN Crossover study.

ANIMALS 10 privately owned dolichocephalic or mesaticephalic dogs free of ophthalmic disease.

PROCEDURES Dogs were randomly assigned to receive doxycycline hyclate first at 5 mg/kg (2.3 mg/lb) or 10 mg/kg (4.5 mg/lb), PO, every 12 hours for 5 days, beginning on day 1. Doxycycline was administered 1 hour prior to feeding. Tear samples were collected from days 1 through 10 approximately 3 hours after the morning dose was administered. Following a 3-week washout period, dogs received the alternative dose in the same conditions. Doxycycline concentration in tear samples from 1 eye (same eye used for both sessions) was measured via liquid chromatography–mass spectrometry and compared between the 2 doxycycline doses.

RESULTS Doxycycline was detected in tear samples of all dogs from days 1 through 10 for both doxycycline doses. Median peak doxycycline concentrations for the 5 mg/kg and 10 mg/kg doses were 2.19 ng/mL on day 3 and 4.32 ng/mL on day 4, respectively. Concentrations differed significantly with time, but this difference was not influenced by dose, dose order, or eye. A significant positive correlation was identified between doxycycline concentration and body weight (r = 0.22).

CONCLUSIONS AND CLINICAL RELEVANCE Detectable doxycycline concentrations were achieved in the tear film of ophthalmologically normal dogs following oral administration of doxycycline at 5 or 10 mg/kg, every 12 hours. Dose had no significant effect on tear film concentration of the drug.

Contributor Notes

Dr. Hamor's present address is Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, Gainsville, FL 32610.

Address correspondence to Dr. Hamor (hamor@ufl.edu).