Literature DB >> 15103209

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

David Goldblum1, Kaspar Rohrer, Beatrice E Frueh, Regula Theurillat, Wolfgang Thormann, Stefan Zimmerli.   

Abstract

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. Copyright 2004 S. Karger AG, Basel

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Year:  2004        PMID: 15103209     DOI: 10.1159/000077331

Source DB:  PubMed          Journal:  Ophthalmic Res        ISSN: 0030-3747            Impact factor:   2.892


  4 in total

Review 1.  [Strategies for antifungal treatment failure in intensive care units].

Authors:  C Arens; M Bernhard; C Koch; A Heininger; D Störzinger; T Hoppe-Tichy; M Hecker; B Grabein; M A Weigand; C Lichtenstern
Journal:  Anaesthesist       Date:  2015-09       Impact factor: 1.041

2.  Toxicities and pharmacokinetics of subconjunctival injection of liposomal amphotericin B.

Authors:  Yuichi Kaji; Erika Yamamoto; Takahiro Hiraoka; Tetsuro Oshika
Journal:  Graefes Arch Clin Exp Ophthalmol       Date:  2008-11-29       Impact factor: 3.117

Review 3.  Tissue penetration of antifungal agents.

Authors:  Timothy Felton; Peter F Troke; William W Hope
Journal:  Clin Microbiol Rev       Date:  2014-01       Impact factor: 26.132

Review 4.  Preclinical Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antifungal Activity of Liposomal Amphotericin B.

Authors:  Jill Adler-Moore; Russell E Lewis; Roger J M Brüggemann; Bart J A Rijnders; Andreas H Groll; Thomas J Walsh
Journal:  Clin Infect Dis       Date:  2019-05-02       Impact factor: 9.079

  4 in total

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