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Antimicrobial Agents and Chemotherapy, December 2002, p. 3719-3723, Vol. 46, No. 12
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.12.3719-3723.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Ocular Distribution of Intravenously Administered Lipid Formulations of Amphotericin B in a Rabbit Model

David Goldblum,1 Kaspar Rohrer,1,2 Beatrice E. Frueh,1 Regula Theurillat,2 Wolfgang Thormann,2 and Stefan Zimmerli3*

Department of Ophthalmology,1 Department of Clinical Pharmacology,2 and Institute for Infectious Diseases, University of Bern, Bern, Switzerland3

Received 14 February 2002/ Returned for modification 18 May 2002/ Accepted 15 August 2002

Little is known about the ocular penetration of amphotericin B (AMB) and its lipid formulations, the current drug of choice in fungal endophthalmitis. The ocular distribution of AMB lipid complex (ABLC), liposomal AMB (L-AMB), and AMB deoxycholate (D-AMB) was studied in a rabbit model. D-AMB (1 mg/kg of body weight/day), ABLC (5 mg/kg/day), or L-AMB (5 mg/kg/day) was given intravenously to rabbits as a single dose or as repeated daily doses on 7 consecutive days after induction of unilateral uveitis by intravitreal injection of endotoxin. AMB concentrations in aqueous humor, vitreous humor, and plasma were determined by high-pressure liquid chromatography 16 h after administration of a single dose or 24 h after the last of seven doses. After single-dose administration, L-AMB achieved at least eightfold-higher AMB concentrations in the aqueous of inflamed eyes than ABLC or D-AMB (1.21 ± 0.58 µg/ml versus 0.14 ± 0.04 and 0.11 ± 0.09 µg/ml, respectively). At that time point no drug was detectable in the vitreous. After 7 days of treatment, the concentration of AMB in the vitreous was higher after treatment with L-AMB (0.47 ± 0.21 µg/ml) than after treatment with ABLC (0.27 ± 0.18 µg/ml) and D-AMB (0.16 ± 0.04 µg/ml). Similarly, AMB concentration in the aqueous was higher after repeated doses of L-AMB (0.73 ± 0.43 µg/ml) than after repeated doses of ABLC (0.03 ± 0.02 µg/ml) or D-AMB (0.13 ± 0.06 µg/ml). No AMB was detected in noninflamed eyes. Following systemic administration, AMB distribution to the eye is inflammation dependent and occurs sequentially, first to the aqueous and then to the vitreous. Compared to D-AMB and ABLC, L-AMB reaches higher drug concentrations in both ocular compartments.

* Corresponding author. Mailing address: Institute for Infectious Diseases, University of Bern, Friedbuehlstr. 51, CH-3010 Bern, Switzerland. Phone: 41 31 632 32 58. Fax: 41 31 632 35 50. E-mail: stefan.zimmerli{at}ifik.unibe.ch.

Antimicrobial Agents and Chemotherapy, December 2002, p. 3719-3723, Vol. 46, No. 12
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.12.3719-3723.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.





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