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...

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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:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/eac28f37e5a64f3cbec381fa8cdf6c8e
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spelling	oai:doaj.org-article:eac28f37e5a64f3cbec381fa8cdf6c8e2021-12-02T20:21:31ZDetermination of therapeutic equivalence of generic products of gentamicin in the neutropenic mouse thigh infection model.1932-620310.1371/journal.pone.0010744https://doaj.org/article/eac28f37e5a64f3cbec381fa8cdf6c8e2010-05-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20505762/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<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.Andres F ZuluagaMaria AgudeloJohn J CardeñoCarlos A RodriguezOmar VesgaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 5, p e10744 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Andres F Zuluaga Maria Agudelo John J Cardeño Carlos A Rodriguez Omar Vesga Determination of therapeutic equivalence of generic products of gentamicin in the neutropenic mouse thigh infection model.
description	<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.
format	article
author	Andres F Zuluaga Maria Agudelo John J Cardeño Carlos A Rodriguez Omar Vesga
author_facet	Andres F Zuluaga Maria Agudelo John J Cardeño Carlos A Rodriguez Omar Vesga
author_sort	Andres F Zuluaga
title	Determination of therapeutic equivalence of generic products of gentamicin in the neutropenic mouse thigh infection model.
title_short	Determination of therapeutic equivalence of generic products of gentamicin in the neutropenic mouse thigh infection model.
title_full	Determination of therapeutic equivalence of generic products of gentamicin in the neutropenic mouse thigh infection model.
title_fullStr	Determination of therapeutic equivalence of generic products of gentamicin in the neutropenic mouse thigh infection model.
title_full_unstemmed	Determination of therapeutic equivalence of generic products of gentamicin in the neutropenic mouse thigh infection model.
title_sort	determination of therapeutic equivalence of generic products of gentamicin in the neutropenic mouse thigh infection model.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/eac28f37e5a64f3cbec381fa8cdf6c8e
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Determination of therapeutic equivalence of generic products of gentamicin in the neutropenic mouse thigh infection model.

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