Determination of therapeutic equivalence of generic products of gentamicin in the neutropenic mouse thigh infection model

ABSTRACT: Background: Drug regulatory agencies (DRA) support prescription of generic products of intravenous antibiotics assuming therapeutic equivalence from pharmaceutical equivalence. Recent reports of deaths associated with generic heparin and metoprolol have raised concerns about the efficacy and safety of DRA-approved drugs. Methodology/Principal Findings: To challenge the assumption that pharmaceutical equivalence predicts therapeutic equivalence, we determined in vitro and in vivo the efficacy of the innovator product and 20 pharmaceutically equivalent generics of gentamicin. The data showed that, while only 1 generic product failed in vitro (MIC = 45.3 vs. 0.7 mg/L, P,0.05), 10 products (including gentamicin reference powder) failed in vivo against E. coli due to significantly inferior efficacy (Emax = 4.81 to 5.32 vs. 5.99 log10 CFU/g, P#0.043). Although the design lacked power to detect differences in survival after thigh infection with P. aeruginosa, dissemination to vital organs was significantly higher in animals treated with generic gentamicin despite 4 days of maximally effective treatment. Conclusion: Pharmaceutical equivalence does not predict therapeutic equivalence of generic gentamicin. Stricter criteria based on solid experimental evidence should be required before approval for human use.

• Autores: Zuluaga Salazar, Andrés Felipe; Agudelo Pérez, María; Rodríguez Jaramillo, Carlos Andrés; Vesga Meneses, Omar; Cárdeno Sánchez, John Jairo
• Tipo de recurso: Article of investigation
• Fecha de publicación: 2010
• Institución: Universidad de Antioquia
• Repositorio: Repositorio UdeA
• Idioma: eng
• OAI Identifier: oai:bibliotecadigital.udea.edu.co:10495/39095
• Acceso en línea: https://hdl.handle.net/10495/39095
• Palabra clave: Antiinfecciosos; Anti-Infective Agents; Infecciones Bacterianas - Complicaciones; Bacterial Infections - complications; Modelos Animales de Enfermedad; Disease Models, Animal; Medicamentos Genéricos; Drugs, Generic; Gentamicinas; Gentamicins; Pruebas de Sensibilidad Microbiana; Microbial Sensitivity Tests; Neutropenia; Organ Specificity; Equivalencia Terapéutica; Therapeutic Equivalency; Muslo; Thigh; Especificidad de Órganos; https://id.nlm.nih.gov/mesh/D000890; https://id.nlm.nih.gov/mesh/D001424; https://id.nlm.nih.gov/mesh/D004195; https://id.nlm.nih.gov/mesh/D016568; https://id.nlm.nih.gov/mesh/D005839; https://id.nlm.nih.gov/mesh/D008826; https://id.nlm.nih.gov/mesh/D009503; https://id.nlm.nih.gov/mesh/D009928; https://id.nlm.nih.gov/mesh/D013810; https://id.nlm.nih.gov/mesh/D013848
• Rights: openAccess
• License: http://creativecommons.org/licenses/by/2.5/co/