Pharmacokinetics and safety of intravitreal caspofungin.

Pharmacokinetics and safety of intravitreal caspofungin.

Antimicrob Agents Chemother. 2014 Sep 22;

Authors: Shen YC, Liang CY, Wang CY, Lin KH, Hsu MY, Yuen HL, Wei LC

Abstract
PURPOSE: Caspofungin exhibits potent antifungal activities against Candida and Aspergillus species. The elimination rate and retinal toxicity of caspofungin were determined in this study to assess its pharmacokinetics and safety in the treatment of fungal endophthalmitis.
METHODS: Intravitreal injections of 50 μg/0.1 mL of caspofungin were administered to rabbits. Vitreous and aqueous humor levels of caspofungin were determined using high performance liquid chromatography (HPLC) at selected time intervals (10 minutes and 1, 2, 4, 8, 16, 24, and 48 hours) and the half-lives were calculated. Eyes were intravitreally injected with caspofungin to obtain the concentrations of 10 ug/mL, 50 ug/mL, 100 ug/mL, and 200 ug/mL. Electroretinograms were recorded 4 weeks after injections, and the injected eyes were examined histologically.
RESULTS: The concentrations of intravitreal caspofungin at various time points exhibited an exponential decay with a half-life of 6.28 hours. The mean vitreous concentration was 6.06 ± 1.76 μg/mL 1 hour after intravitreal injection, and this declined to 0.47 ± 0.15 μg/mL at 24 hours. The mean aqueous concentration showed undetectable levels at all time points. There were no statistical differences in scotopic a-wave and b-wave responses between control eyes and caspofungin-injected eyes. No focal necrosis or other abnormality in retinal histology was observed.
CONCLUSIONS: Intravitreal caspofungin injection may be considered to be an alternative treatment of fungal endophthalmitis based on its antifungal activity, lower retinal toxicity, and slower elimination rate in the vitreous. More clinical data are needed to determine its potential role as primary therapy for fungal endophthalmitis.

PMID: 25246398 [PubMed - as supplied by publisher]