Document Detail

Intravitreal voriconazole: in vitro safety-profile for fungal endophthalmitis.
MedLine Citation:
PMID:  18997637     Owner:  NLM     Status:  MEDLINE    
INTRODUCTION: Fungal endophthalmitis is a rare but sight-threatening disease. Despite an expanding range of fungal pathogens, there are only few therapeutic agents for its treatment available. Voriconazole is a second-generation synthetic triazole with a broad action against yeasts and molds. The current study investigates the safety of Voriconazole for intravitreal application in a cell culture model. METHODS: Primary human retinal pigment epithelium cells (RPE) and primary human optic nerve head astrocytes were treated with concentrations of Voriconazole ranging from 25 microg/mL to 10 mg/mL. Possible toxic effects and IC50 were evaluated after 24 hours and under conditions of oxidative stress. By treating the RPE cell lines with tumor-necrosisfactor alpha (TNF-alpha), lipopolysaccharides (LPS), and interleukin-6 (IL-6) the effects of Voriconazole on cellular viability under conditions of inflammation were investigated. Toxicity was evaluated by colorimetric measuring the inhibition of RPE cell proliferation (MTT). Additionally cell viability was quantified by a microscopic live-dead-assay. RESULTS: Concentrations <250 microg/mL Voriconazole had no influence neither on RPE nor on optic nerve head astrocytes cell proliferation and cell viability when administered for 24 hours and under oxidative stress. When preincubated with tumor-necrosis-factor alpha, lipopolysaccharides and interleukin-6 for 24 hours and subsequently treated with Voriconazole at concentrations up to 250 microg/mL for 24 hours no significant decrease in proliferation and viability was observed. CONCLUSIONS: This study showed that no significant toxicity existed for Voriconazole in vitro on primary RPE and optic nerve head astrocytes when administered in therapeutic concentrations up to 250 microg/mL.
Marcus Kernt; Aljoscha S Neubauer; Herminia Mino De Kaspar; Anselm Kampik
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Retina (Philadelphia, Pa.)     Volume:  29     ISSN:  1539-2864     ISO Abbreviation:  Retina (Philadelphia, Pa.)     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-03-18     Completed Date:  2009-05-26     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8309919     Medline TA:  Retina     Country:  United States    
Other Details:
Languages:  eng     Pagination:  362-70     Citation Subset:  IM    
Department of Ophthalmology, Ludwig Maximilian University, Munich, Germany.
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MeSH Terms
Antifungal Agents / administration & dosage*,  pharmacokinetics
Cell Proliferation / drug effects
Cells, Cultured
Endophthalmitis / drug therapy*,  metabolism,  pathology
Eye Infections, Fungal / drug therapy*,  metabolism,  pathology
Middle Aged
Oxidative Stress
Pyrimidines / administration & dosage*,  pharmacokinetics
Retinal Pigment Epithelium / drug effects,  metabolism,  pathology
Treatment Outcome
Triazoles / administration & dosage*,  pharmacokinetics
Vitreous Body
Reg. No./Substance:
0/Antifungal Agents; 0/Pyrimidines; 0/Triazoles; 0/voriconazole

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