Amphotericin B remains an important
antifungal agent in the treatment of
ocular mycosis. Since topical ocular application is limited because of ocular irritation and poor penetration, we studied the pharmacokinetics of
amphotericin B encapsulated in
unilamellar liposomes (
AmBisome). One drop (20 microliters) of
AmBisome or an equivalent concentration of
amphotericin B was applied to rabbit eyes.
Drug concentrations were measured 15, 60, 120 and 240 min following administration of the agents by HPLC in cornea and aqueous humor. The effect of intact (group A) and debrided corneal epithelium (group B) was also studied. Corneal
amphotericin B levels were significantly higher (P < 0.01) after 15 min in animals receiving
amphotericin B as compared to
AmBisome in group A. At later time points no differences in the corneal
drug levels were found, and the
drug levels following
AmBisome application were remarkably stable. Epithelial removal resulted in increased corneal
drug levels following application of both
amphotericin B preparations. Significantly higher
drug levels were observed after free
amphotericin B treatment at 15-60 min (P < 0.01).
Drug levels in the aqueous humor did not differ between the two
amphotericin B preparations and remained below therapeutically effective concentrations. These results suggest that topically delivered
AmBisome provides stable corneal
drug levels, but has the potential benefit of lowered
ocular toxicity.