title: Kinetics of uptake and effects of topical indomethacin application on protein concentration in the aqueous humor of dogs.
abstract: The pharmacokinetic properties of indomethacin and its effects on aqueous protein values were studied in 15 clinically normal Beagles. The dogs were treated every 6 hours with 1% indomethacin suspension in 1 eye, with the other eye serving as a control. After 24 hours, the dogs were anesthetized and samples of aqueous humor (AH) were drawn by aqueocentesis at 0, 15, 30, 60, and 90 minutes after initial paracentesis. Additional samples were drawn at the time of euthanasia, 180 (6 dogs) and 360 minutes (9 dogs) minutes after initial paracentesis. Blood samples were obtained at each treatment and at each aqueocentesis. The eyes were enucleated after dogs were euthanatized. Aqueous protein concentrations and indomethacin concentrations in AH, plasma, and different ocular tissues were determined. Topical indomethacin administration had no effect on baseline protein concentrations of AH. It reduced protein concentrations in AH significantly at all times after initial aqueocentesis. This reduction was approximately 30%. Indomethacin in the AH is mostly protein-bound. Concentrations were 350 ng/ml in primary AH and 1,305 ng/ml in secondary AH, 90 minutes after initial aqueocentesis. Free-drug concentrations were relatively constant at about 220 ng/ml. Indomethacin administered topically is readily absorbed by the ocular adnexae, reaching a steady-state concentration of 25 ng/ml in blood plasma 18 hours after the start of treatment. Plasma concentrations were 50 times lower than therapeutically effective concentrations. High indomethacin concentrations were found in the cornea only. Low concentrations were found in the iris and ciliary body, the lens, and in the choroid.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Veterinary Surgical Clinic, University of Zurich, Switzerland.
authors.forename: B M
authors.initials: BM
authors.lastname: Spiess
authors.forename: G A
authors.initials: GA
authors.lastname: Mathis
authors.forename: K L
authors.initials: KL
authors.lastname: Franson
authors.forename: A
authors.initials: A
authors.lastname: Leber
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001082:Aqueous Humor / Q000737:chemistry / Q000378:metabolism*; D004285:Dogs / Q000378:metabolism*; D005136:Eye Proteins / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D007213:Indomethacin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male
chemical_list: D005136:Eye Proteins; D007213:Indomethacin