K. Klippenstein et al., THE QUALITATIVE EVALUATION OF THE PHARMACOKINETICS OF SUBCONJUNCTIVALLY INJECTED ANTIFUNGAL AGENTS IN RABBITS, Cornea, 12(6), 1993, pp. 512-516
Dutch-belted rabbits with corneal epithelium either intact or debrided
were injected subconjunctivally with 300 mul of one of six antifungal
agents: 10 mg/ml miconazole, 5 mg/ml fluconazole, 5 mg/ml ketoconazol
e, 2.5 mg/ml itraconazole, and 5 mg/ml amphotericin B. At intervals of
10 min to 96 h after injection, animals were killed and corneas remov
ed at the limbus. Three vertical strips from the right cornea and four
contiguous 3-mm disks trephined from the central vertical axis of the
left cornea were placed on agar plates seeded with an appropriate ind
icator organism. After 24 h of incubation, the zones of inhibition wer
e measured. For itraconazole, miconazole, fluconazole, saperconazole,
and ketoconazole, central corneal levels peaked by 2 h in normal and d
ebrided corneas. Little or no drug was detectable after 4-8 h, except
for itraconazole, which persisted in the cornea for at least 24 h in b
oth normal and debrided corneas. Peak levels of amphotericin B in the
central cornea were achieved after 2 h in rabbits with debrided cornea
s, with no drug activity measured after 8 h. There were no detectable
levels of drug found in the central corneas of rabbits with intact cor
neal epithelium. On the basis of this pilot study, the method offers a
rapid approach to the screening of antifungal agents for possible use
by subconjunctival injection.