Toxicity and Pharmacokinetics of Intrastromal Injection of Amphotericin B in a Rabbit Model

Abstract

Purpose: 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 than10 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.

• Amphotericin B
• intrastromal injection
• ocular toxicity
• pharmacokinetics

Notes

*This paper has not been presented in a conference in part or in whole in any language.