title: Ocular distribution of cyclosporin A (Sandimmun) following systemic and topical administration to rabbits.
abstract: The purpose of this study was to determine the distribution of cyclosporin A (CsA) in various ocular fluids and tissues in the rabbit by two routes of administration. CsA was administered to two groups of two rabbits either by intramuscular route at a dose of 25 mg/kg/day or by local route using eyedrops, at a dose of 10 mg/day (-2.8 mg/kg/day) for eight days. An extra animal was treated with a placebo solution in each group in order to obtain control values. Samples of blood and tears were collected throughout the 8-day treatment period. On day 9, the six animals were sacrificed and additional samples were collected from the vitreous body, the aqueous humor, the cornea and the globe. The concentrations of CsA were determined by RIA using the specific monoclonal antibody contained in the Sandimmun-kit. After administration by intramuscular route, high concentrations of CsA were detected in the blood. Within the eye, this compound was clearly detected in the tears, the cornea and the globe, and was suspected in the vitreous body and the aqueous humor. After administration by local route, using eyedrops, no CsA was detected in the blood, the vitreous body or the aqueous humor. However, despite doses ten times lower than those administered by the intramuscular route, this compound was clearly detected in the tears, the cornea and the globe of the treated eye. Moreover, similar concentrations were obtained in the untreated eye. These data reveal a real passage of CsA from the left treated eye to the right untreated eye.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Pharmaceutical Research Centre, Sandoz Laboratories, Rueil-Malmaison, France.
authors.forename: L
authors.initials: L
authors.lastname: Vernillet
authors.forename: R L
authors.initials: RL
authors.lastname: Lundh
authors.forename: F
authors.initials: F
authors.lastname: Acezat-Mispelter
authors.forename: C
authors.initials: C
authors.lastname: Goizel
authors.forename: H
authors.initials: H
authors.lastname: Humbert
authors.forename: Y
authors.initials: Y
authors.lastname: Pouliquen
mesh_terms: D000287:Administration, Topical; D000818:Animals; D003315:Cornea / Q000378:metabolism; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005123:Eye / Q000378:metabolism*; D007273:Injections, Intramuscular; D008297:Male; D009883:Ophthalmic Solutions; D011817:Rabbits; D013666:Tears / Q000378:metabolism; D014822:Vitreous Body / Q000378:metabolism
chemical_list: D009883:Ophthalmic Solutions; D016572:Cyclosporine