Demonstration of Therapeutic Equivalence of Fluconazole Generic Products in the Neutropenic Mouse Model of Disseminated Candidiasi

ABSTRACT: Some generics of antibacterials fail therapeutic equivalence despite being pharmaceutical equivalents of their innovators, but data are scarce with antifungals. We used the neutropenic mice model of disseminated candidiasis to challenge the therapeutic equivalence of three generic products of fluconazole compared with the innovator in terms of concentration of the active pharmaceutical ingredient, analytical chemistry (liquid chromatography/mass spectrometry), in vitro susceptibility testing, single-dose serum pharmacokinetics in infected mice, and in vivo pharmacodynamics. Neutropenic, five week-old, murine pathogen free male mice of the strain Udea:ICR(CD-2) were injected in the tail vein with Candida albicans GRP-0144 (MIC = 0.25 mg/L) or Candida albicans CIB-19177 (MIC = 4 mg/L). Subcutaneous therapy with fluconazole (generics or innovator) and sterile saline (untreated controls) started 2 h after infection and ended 24 h later, with doses ranging from no effect to maximal effect (1 to 128 mg/kg per day) divided every 3 or 6 hours. The Hill’s model was fitted to the data by nonlinear regression, and results from each group compared by curve fitting analysis. All products were identical in terms of concentration, chromatographic and spectrographic profiles, MICs, mouse pharmacokinetics, and in vivo pharmacodynamic parameters. In conclusion, the generic products studied were pharmaceutically and therapeutically equivalent to the innovator of fluconazole.

• Autores: González Pérez, Javier Mauricio; Rodríguez Jaramillo, Carlos Andrés; Zuluaga Salazar, Andrés Felipe; Agudelo Pérez, María; Vesga Meneses, Omar
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2015
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/39094
• Acceso en línea: https://hdl.handle.net/10495/39094
• Palabra clave: Antifúngicos; Antifungal Agents; Área Bajo la Curva; Area Under Curve; Candida albicans; Candidiasis; Cromatografía Líquida de Alta Presión; Chromatography, High Pressure Liquid; Modelos Animales de Enfermedad; Disease Models, Animal; Medicamentos Genéricos; Drugs, Generic; Fluconazol; Fluconazole; Equivalencia Terapéutica; Therapeutic Equivalency; https://id.nlm.nih.gov/mesh/D000935; https://id.nlm.nih.gov/mesh/D019540; https://id.nlm.nih.gov/mesh/D002176; https://id.nlm.nih.gov/mesh/D002177; https://id.nlm.nih.gov/mesh/D002851; https://id.nlm.nih.gov/mesh/D004195; https://id.nlm.nih.gov/mesh/D016568; https://id.nlm.nih.gov/mesh/D015725; https://id.nlm.nih.gov/mesh/D013810
• Rights: openAccess
• License: https://creativecommons.org/licenses/by/4.0/