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

<h4>Background</h4>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 e...

Descripción completa

Guardado en:
Detalles Bibliográficos
Autores principales: Andres F Zuluaga, Maria Agudelo, John J Cardeño, Carlos A Rodriguez, Omar Vesga
Formato: article
Lenguaje:EN
Publicado: Public Library of Science (PLoS) 2010
Materias:
R
Q
Acceso en línea:https://doaj.org/article/eac28f37e5a64f3cbec381fa8cdf6c8e
Etiquetas: Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
Descripción
Sumario:<h4>Background</h4>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.<h4>Methodology/principal findings</h4>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 (E(max) = 4.81 to 5.32 vs. 5.99 log(10) CFU/g, P<or =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.<h4>Conclusion</h4>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.