Corneal concentrations following systemic administration of amphotericin B and its lipid preparations in a rabbit model.
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.


CONCLUSIONS
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.
Goldblum
David
D
Department of Ophthalmology, University of Bern, Bern, Switzerland. david.goldblum@insel.ch
Rohrer
Kaspar
K
Frueh
Beatrice E
BE
Theurillat
Regula
R
Thormann
Wolfgang
W
Zimmerli
Stefan
S
D000666:Amphotericin B / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D003315:Cornea / Q000378:metabolism*; D003840:Deoxycholic Acid / Q000493:pharmacokinetics*; D004334:Drug Administration Schedule; D004338:Drug Combinations; D005260:Female; D008297:Male; D009994:Osmolar Concentration; D010713:Phosphatidylcholines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D010715:Phosphatidylglycerols / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011817:Rabbits; D014605:Uveitis / Q000378:metabolism*
D000935:Antifungal Agents; D004338:Drug Combinations; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C068538:liposomal amphotericin B; D003840:Deoxycholic Acid; D000666:Amphotericin B; C059765:amphotericin B, deoxycholate drug combination