Systemic absorption and adverse ocular and systemic effects after topical ophthalmic administration of 0.1% diclofenac to healthy cats

• Kimberly ^[5] ; Chantale ^[1] ; Ron ^[2] ; Dana ^[3] ; Butch ^[4] ; Stephanie ^[6]
  1. [1] L. Pinard
  2. [2] J. Johnson
  3. [3] G. Allen
  4. [4] K. KuKanich
  5. [5] K. Hsu
  6. [6] G. Nykamp

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• Localización: American Journal of Veterinary Research, ISSN-e 1943-5681, ISSN 0002-9645, Vol. 76, Nº. 3, 2015, págs. 253-265
• Idioma: inglés
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  • Systemic absorption and adverse ocular and systemic effects after topical ophthalmic administration of 0.1% diclofenac to healthy cats Kimberly K. Hsu DVM, MSc; Chantale L. Pinard DVM, MSc; Ron J. Johnson DVM, PhD; Dana G. Allen DVM, MSc; Butch K. KuKanich DVM, PhD; Stephanie G. Nykamp DVM Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada. (Hsu, Pinard, Allen, Nykamp); Department of Biomedical Sciences, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada. (Johnson); Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506. (KuKanich) Dr. Hsu's present address is Eye Care for Animals, 372 S Milwaukee Ave, Wheeling, IL 60090.

    Address correspondence to Dr. Hsu (khsu@eyecareforanimals.com).

    OBJECTIVE To quantify plasma concentrations and determine adverse ocular, renal, or hepatic effects associated with repeated topical ophthalmic application of 0.1% diclofenac to healthy cats.

    ANIMALS 8 healthy sexually intact male cats.

    PROCEDURES A randomized, placebo-controlled crossover study was conducted. A topical formulation of 0.1% diclofenac was administered 4 times/d for 7 days to 4 cats, and artificial tear (control) solution was administered to the other 4 cats. After a 12-day washout period, cats received the other treatment. Ophthalmic examinations were performed daily. Plasma samples were obtained on days 1 and 7 for pharmacokinetic analysis. A CBC, serum biochemical analysis, urinalysis, determination of urine protein-to-creatinine ratio, and determination of glomerular filtration rate were performed before the start of the study and after each 7-day treatment period.

    RESULTS Mild conjunctival hyperemia was the only adverse ocular effect detected. Maximal drug concentration and area under the curve were significantly higher on day 7 than on day 1. Diclofenac-treated cats had a significantly lower glomerular filtration rate than did control-treated cats after the second but not after the first treatment period, presumably associated with iatrogenic hypovolemia.

    CONCLUSIONS AND CLINICAL RELEVANCE Topical ophthalmic administration of 0.1% diclofenac was well tolerated in healthy cats, with only mild signs of ocular irritation. Detectable systemic concentrations of diclofenac were achieved with accumulation over 7 days. Systemic absorption of diclofenac may be associated with reduced glomerular filtration rate, particularly in volume-contracted animals. Topical ophthalmic 0.1% diclofenac should be used with caution in volume-contracted or systemically ill cats.