Ocular pharmacokinetics of saperconazole in rabbits. A potential agent against keratomycoses
D. M. O'Day, W. S. Head, R. D. Robinson, T. E. Williams and R. Wolff
Department of Ophthalmology, Vanderbilt University School of Medicine, Nashville, Tenn.
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 debrided 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
debrided 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 debrided corneas, were a third higher than those
following topical therapy in debrided 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.