Toxicity and pharmacokinetics of intrastromal injection of amphotericin B in a rabbit model.
OBJECTIVE
To investigate the ocular toxicity and pharmacokinetics of intrastromal injection of amphotericin B (AmB) in a rabbit model.


METHODS
Forty albino rabbits were randomly divided into five groups (eight per group). The rabbits were anesthetized before they received the medication. Intrastromal injection of 0.1 ml balanced salt solution containing 0, 5, 10, 20 or 30 μg of AmB was performed on eyes of each group five times (once per four days), respectively. The presence of possible corneal clouding, epithelial erosion and corneal neovascularization was monitored with a slit-lamp biomicroscope. Corneal ultrasonic pachymetry was used to detect the corneal thickness of intrastromal-injected eyes. Thirty days after the last injection, the corneal transparency as well as the number and ultrastucture of corneal endothelial cells were examined. The concentrations of the AmB in the cornea and aqueous humor were evaluated at 30 min, 6 h and at 1, 3 and 7 days after the intrastromal injection of 10 µg AmB.


RESULTS
Intrastromal injection of AmB at concentrations of 5 and 10 μg per 0.1 ml did not induce obvious toxicity to the cornea when compared with the controls. However, when the concentration of AmB increased to 20 μg per 0.1 ml or more, corneal edema, corneal epithelial erosion and severe neovascularization appeared. A single intrastromal injection of 10 μg AmB achieved an effective drug level in corneas which was maintained for up to 7 days.


CONCLUSIONS
Intrastromal injection of AmB at a concentration of less than 10 μg per 0.1 ml is safe to the rabbit corneas. Intrastromal injection of AmB may be an adjunctive treatment for deep recalcitrant fungal keratitis.
Southwest Eye Hospital/Southwest Hospital, Third Military Medical University , Chongqing , People's Republic of China and.
Linghui
L
Qu
Liangmao
L
Li
Hanping
H
Xie
D000666:Amphotericin B / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D001082:Aqueous Humor / Q000378:metabolism*; D016510:Corneal Neovascularization / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D003319:Corneal Stroma; D004195:Disease Models, Animal; D015821:Eye Infections, Fungal / Q000188:drug therapy; D007267:Injections; D007634:Keratitis / Q000188:drug therapy; D011817:Rabbits
D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D000666:Amphotericin B