Resumen de Systemic absorption and adverse ocular and systemic effects after topical ophthalmic administration of 0.1% diclofenac to healthy cats
Kimberly K. Hsu, Chantale L. Pinard, Bob Johnson, Dana G. Allen, Butch KuKanich, Stephanie G Nykamp
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.
