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Updated: Aug 24, 2026
Use of Rabbit Eyes in Pharmacokinetic Studies of Intraocular Drugs
Published on: July 23, 2016
Corneal concentrations following systemic administration of amphotericin B and its lipid preparations in a rabbit
David Goldblum1, Kaspar Rohrer, Beatrice E Frueh
1Department of Ophthalmology, University of Bern, Bern, Switzerland. david.goldblum@insel.ch
Background:
Amphotericin B (AmB) and various lipid formulations of AmB are available for the treatment of fungal infections of the eye. Currently, the recommended route of administration for the treatment of fungal keratitis is by topical application. Nevertheless, because of the risk of a difficult to treat exogenous fungal endophthalmitis, a combined topical and systemic treatment is frequently given when treating deep fungal keratitis. To date, little is known about the pure corneal availability of these drugs following systemic treatment. In this study, the corneal concentration following 7 daily doses of parenteral AmB lipid complex (ABLC) or liposomal AmB (L-AmB) was compared to that of AmB deoxycholate (D-AmB) in a rabbit model.
Methods:
Following induction of uveitis in one rabbit eye by intravitreal injection of endotoxin, daily doses of D-AmB (1 mg/kg), ABLC (5 mg/kg) or L-AmB (5 mg/kg) were given intravenously on 7 consecutive days. Five or more rabbits per treatment were used. AmB concentrations were determined by high-performance liquid chromatography (HPLC) in corneas collected at autopsy 24 h after the 7th and final dose. Data were analyzed using the Mann-Whitney U test.
Results:
After 7 days of treatment, mean corneal concentrations of AmB in the inflamed eyes were significantly higher (2.38 +/- 1.47 microg/g; p < 0.01) following treatment with L-AmB compared with ABLC (<0.1 microg/g) and D-AmB (0.46 +/- 0.2 microg/g). No AmB could be detected in the corneas of the non-inflamed eyes.
Conclusion:
In our rabbit model, AmB penetration into the cornea was significantly higher after systemic administration of L-AmB compared with conventional D-AmB or ABLC.
Insights
Systemic liposomal amphotericin B (L-AmB) showed significantly higher corneal drug concentrations compared to conventional amphotericin B deoxycholate (D-AmB) and amphotericin B lipid complex (ABLC) in a rabbit model of fungal keratitis.
Area of Science:
- Ophthalmology
- Mycology
- Pharmacology
Background:
- Amphotericin B (AmB) formulations are used for ocular fungal infections.
- Topical application is standard for fungal keratitis, but systemic treatment is often combined for deep infections.
- Corneal drug availability after systemic administration is not well understood.
Purpose of the Study:
- To compare corneal drug concentrations of systemic amphotericin B deoxycholate (D-AmB), amphotericin B lipid complex (ABLC), and liposomal amphotericin B (L-AmB).
- To evaluate corneal penetration following systemic administration in a rabbit model.
Main Methods:
- Rabbits with induced uveitis received daily intravenous doses of D-AmB, ABLC, or L-AmB for 7 days.
- AmB concentrations in corneal tissue were measured using high-performance liquid chromatography (HPLC).
- Corneas were collected 24 hours after the final dose.
Main Results:
- Mean corneal AmB concentrations were significantly higher with L-AmB treatment compared to ABLC and D-AmB.
- L-AmB treatment resulted in mean corneal concentrations of 2.38 microg/g, while ABLC had <0.1 microg/g and D-AmB had 0.46 microg/g.
- No AmB was detected in corneas of non-inflamed eyes.
Conclusions:
- Systemic L-AmB demonstrates superior corneal penetration compared to D-AmB and ABLC in this rabbit model.
- These findings suggest L-AmB may be a more effective systemic option for treating deep fungal keratitis.
