title: Ocular pharmacokinetics of saperconazole in rabbits. A potential agent against keratomycoses.
abstract: The ocular pharmacokinetics of saperconazole, an experimental lipophilic triazole with activity against filamentous fungi, including Aspergillus and Candida species, were evaluated in rabbits by radioassay. The drug was administered by topical, subconjunctival, and oral routes. Following a single 20-microL drop of 0.25% saperconazole in normal corneas, a mean (+/- SEM) peak level of 2.32 +/- 0.06 micrograms/g was achieved in 10 minutes. In débrided corneas, a peak level of 13.09 +/- 2.87 micrograms/g was achieved in 2 minutes. The drug was rapidly cleared from the cornea within 2 hours. The administration of 13 drops during 1 hour resulted in a threefold increase in normal corneal levels and in a sixfold increase in débrided cornea levels. Peak levels following subconjunctival injection in normal corneas (12.91 +/- 2.02 micrograms/g) were approximately twofold greater than those following sustained topical administration (6.19 +/- 0.16 micrograms/g) and, in débrided corneas, were a third higher than those following topical therapy in débrided corneas. Clearance was virtually complete by 8 hours. Levels following oral administration were low and probably subtherapeutic in all ocular tissues that were evaluated. Bioassay studies revealed that 44.17% of the drug in the cornea following topical administration was bioactive.
authors.affiliation: Department of Ophthalmology, Vanderbilt University School of Medicine, Nashville, Tenn.
authors.forename: D M
authors.initials: DM
authors.lastname: O'Day
authors.forename: W S
authors.initials: WS
authors.lastname: Head
authors.forename: R D
authors.initials: RD
authors.lastname: Robinson
authors.forename: T E
authors.initials: TE
authors.lastname: Williams
authors.forename: R
authors.initials: R
authors.lastname: Wolff
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000818:Animals; D000935:Antifungal Agents / Q000493:pharmacokinetics*; D001393:Azoles / Q000493:pharmacokinetics*; D001682:Biological Availability; D003320:Corneal Ulcer / Q000188:drug therapy / Q000382:microbiology; D005123:Eye / Q000378:metabolism*; D015821:Eye Infections, Fungal / Q000188:drug therapy; D007267:Injections; D011817:Rabbits; D011863:Radioimmunoassay; D014018:Tissue Distribution
chemical_list: D000935:Antifungal Agents; D001393:Azoles; C060571:saperconazole