Penetration of Topically Administered 0.5-Percent Caspofungin Eye Drops into Human Aqueous Humor

Abstract

Ten participants attending elective anterior segment eye surgery received 0.5% caspofungin eye drops either 1 drop hourly for 4 h or 1 drop an hour before surgery. The eye drops were generally well tolerated. In the absence of inflammation or corneal abrasion, topical caspofungin does not achieve clinically relevant concentrations.Fungal keratitis is a potentially blinding condition, with Candida, Aspergillus, and Fusarium spp. (2, 21) being the common pathogens. Current treatment for fungal keratitis is inadequate (8); thus, alternatives are needed.Caspofungin has activity against a wide range of fungi, with MIC 90 values ranging from 60 to 2,000 ng/ml (15, 23). Caspofungin eye drops are effective for treatment of fungal keratitis in rabbits (11, 18) and have good penetration into animal eyes with inflammation or previous corneal abrasion (10, 23). Clinically, caspofungin is administered mostly intravenously (1,4,6,9,19,20) or intravitreally (24) for ocular mycosis. The successful use of topical caspofungin alone (13) or in combination with voriconazole (22) has been reported for two patients. However, the utility of topical caspofungin in fungal keratitis remains unknown, partly due to limited data on its penetration into human aqueous humor after topical administration. This study aimed to investigate the ocular penetration of 0.5% caspofungin eye drops into human aqueous humor.

Treatment of Alternaria Keratitis with Intrastromal and Topical Caspofungin in Combination with Intrastromal, Topical, and Oral Voriconazole

“…32 Our group has recently reported that caspofungin 0.5% eye drops were able to penetrate into intact human eyes due to use of a more sensitive analytical assay (LLOQ = 10 ng/mL) 33 to detect caspofungin in human aqueous humor (concentrations ranging from 28.9 to 95.1 ng/mL). 34 The concentrations observed in our study, however, were mostly below the MIC 90 (0.06-2 µg/mL) required for most fungal species. 35,36 This could be the result of its large molecular weight (1213 Da) and the fact that caspofungin is highly protein bound (96.5%), 37 which limits its penetration into intact eyes.…”

New Formulations Loading Caspofungin for Topical Therapy of Vulvovaginal Candidiasis

“…There are not previous studies reporting the delivery of CSP because is the first time it has been applied topically in vaginal mucosa. Only a topical study of eye drops has been found in the literature [ 30 ].…”

Recent Perspectives in the Management of Fungal Keratitis

“…Several in vitro and in vivo studies have shown promising results with respect to the safety, efficacy and dosage of these agents [143,144]. The studies done in an animal model [145] as well as in human volunteers [146] on the ocular penetration of caspofungin have shown that its penetration is better in an inflamed cornea or if the epithelial layer is denuded. Caspofungin used in concentrations of 1%/0.5% in solution for topical use and intravenous (IV) formulation for systemic use have been reported to have an adjunctive role in the management of ocular fungal infections caused by Alternaria [147,148], voriconazole refractory Candida albicans keratitis [149] and recurrent Candida parapsilosis keratitis [150].…”