title: Systemic absorption and adverse ocular and systemic effects after topical ophthalmic administration of 0.1% diclofenac to healthy cats.
abstract: 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.
  
  
  METHODS
  8 healthy sexually intact male cats.
  
  
  METHODS
  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
  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.
authors.affiliation: Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON N1G 2W1, Canada.
authors.forename: Kimberly K
authors.initials: KK
authors.lastname: Hsu
authors.forename: Chantale L
authors.initials: CL
authors.lastname: Pinard
authors.forename: Ron J
authors.initials: RJ
authors.lastname: Johnson
authors.forename: Dana G
authors.initials: DG
authors.lastname: Allen
authors.forename: Butch K
authors.initials: BK
authors.lastname: KuKanich
authors.forename: Stephanie G
authors.initials: SG
authors.lastname: Nykamp
mesh_terms: D065567:Absorption, Physiological; D060433:Administration, Ophthalmic / Q000662:veterinary; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D002415:Cats / Q000378:metabolism*; D018592:Cross-Over Studies; D004008:Diclofenac / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004311:Double-Blind Method; D005919:Glomerular Filtration Rate / Q000662:veterinary; D008297:Male; D009883:Ophthalmic Solutions / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D014792:Visual Acuity
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D009883:Ophthalmic Solutions; D004008:Diclofenac