ABSTRACT
PURPOSE: The objective of the study is to provide toxicological information through the HET-CAM test of Fluconazole and Voriconazole eye drops prepared commonly in Pharmacy Services for the treatment of fungal keratitis. METHOD: Experimental Study. The ocular toxicity of topical voriconazole 10 mg/ml and fluconazole 2 mg/ml were evaluated by the hen's egg test (HET) on the chorioallantoic membrane (CAM). The effects on blood vessels were based on its behavior during 300 seconds and processes that may occur at each time, then we calculated the irritation index (is, irritation score). RESULTS AND CONCLUSIONS: Both eye drops, voriconazol and fluconazole have been proven to be safe, since the IS that we obtained was zero for both samples and did not present significant signs of irritation. Therefore, these eyedrops are considered suitable for ocular use from a toxicological point of view.
OBJETIVO: El objetivo del estudio es aportar información toxicológica mediante el ensayo HET-CAM, de los colirios de Fluconazol y Voriconazol elaborados de manera habitual en los Servicios de Farmacia para el tratamiento de las queratitis fúngicas. MÉTODOS: Estudio experimental en el que se ensaya la potencial toxicidad ocular del colirio de voriconazol 10 mg/ml y fluconazol 2 mg/ml mediante el método Hen s Egg Test-Chorioallantoic Membrane (HET-CAM). Los resultados se fundamentan en la observación de los posibles procesos dañinos que pudiesen ocurrir en los vasos sanguíneos de la membrana corioalantoidea del embrión de pollo durante un tiempo de contacto de 300 segundos, calculándose posteriormente el índice de irritación (IS, Irritation Score). RESULTADOS Y CONCLUSIONES: Se obtienen IS nulos para ambas muestras, no mostrando por tanto indicios de irritación aguda apreciables, considerándose por tanto aptos para su utilización desde el punto de vista toxicológico.
Subject(s)
Antifungal Agents/toxicity , Eye Diseases/chemically induced , Fluconazole/toxicity , Voriconazole/toxicity , Animals , Chick Embryo , Chorioallantoic Membrane , Eggs , Ophthalmic Solutions , Toxicity Tests/methodsABSTRACT
BACKGROUND: The purpose of this study was to evaluate microspheres of PLGA containing cyclosporin (CsA) as a subconjunctival drug delivery system and to test their efficacy in the prevention of corneal allograft rejection in the rabbit. METHODS: Rabbits were injected subconjunctivally with a solution of CsA (CsA-AR) (20 animals) or a microsphere suspension of CsA (CsA-MP) (20 animals), with equivalent drug concentrations (15 mg/ml). The concentration of CsA in the aqueous, cornea and blood was measured by radioimmunoassay at different times thereafter. In other rabbits, 40 allogeneic grafts were performed. Animals were divided into four groups that received the following subconjunctival treatments: group 1: AR solution (solvents of CsA-AR solution); group 2: CsA-AR solution; group 3: MP suspension (empty microspheres); group 4: CsA-MP suspension. RESULTS: Mean corneal levels of CsA were 1174+/-830, 918+/-179, 972+/-580, 268+/-182 and 243+/-162 ng/ml at 12, 24 and 48 h and 7 and 14 days after the injection of CsA-AR. For the CsA-MP suspension, corneal concentrations were 1195+/-321, 234+/-147 and 88+/-77 ng/ml at 12, 24 and 48 h but subsequently dropped to undetectable levels. Blood and aqueous levels were undetectable. Treatment with CsA significantly improved the survival time and survival rate of grafts in the CsA-treated groups (2, 4) over grafts in non-CsA-treated groups (1, 3). There was no significant difference in the graft survival curve between groups 2 and 4. CONCLUSION: CsA-containing microspheres might be a promising formulation in the prevention of corneal graft rejection. Since the levels of CsA in blood were undetectable, this treatment might avoid the problems associated with systemic side effects.
