Toxicity and pharmacokinetics of subconjunctival amphotericin B. An experimental study

The pharmacokinetics and toxicity of subconjunctival (S/C) amphotericin B (AmB) were evaluated in Dutch-belted rabbits. Following the S/C injection of 1,500 micrograms of AmB, corneal and aqueous levels were determined by bioassay. The highest levels were present in the periphery of debrided corneas at 1 h (90.12 +/- 2.4 micrograms/g). The debrided central cornea contained 30.84 micrograms/g, almost double the amount present in the intact central cornea. These levels were transient; in the central intact cornea only 2.08 micrograms/g could be detected at 2 h. Peak aqueous levels were low (0.95 +/- .24 micrograms/mL in debrided corneas at 1 h). The S/C injection of 1,500 micrograms of AmB in sodium deoxycholate produced a severe inflammatory response in the conjunctiva, episclera, iris, anterior chamber, and superior rectus muscle that persisted 10 days. Injection of sodium deoxycholate alone produced a similar but less severe response.