Determination of Therapeutic Equivalence (TE) of 5 Generic Products (GP) of Penicillin G (PEN) Using the Neutropenic Murine Thigh Infection Model (NMTIM)
ABSTRACT: Background: Legal use of GP in human and veterinary medicine has great impact in price regulation worldwide, but numbers of GP makers are increasing overwhelmingly. Beyond quality problems, concern is growing about the scientific basis of using bioequivalence (BE) as surrogate proof of TE,...
- Autores:
-
Zuluaga Salazar, Andrés Felipe
Agudelo Pérez, María
Salazar Giraldo, Beatriz
Rodríguez Jaramillo, Carlos Andrés
Vesga Meneses, Omar
- Tipo de recurso:
- Article of investigation
- Fecha de publicación:
- 2004
- Institución:
- Universidad de Antioquia
- Repositorio:
- Repositorio UdeA
- Idioma:
- eng
- OAI Identifier:
- oai:bibliotecadigital.udea.edu.co:10495/26412
- Acceso en línea:
- http://hdl.handle.net/10495/26412
- Palabra clave:
- Penicilina G
Penicillin G
Medicamentos Genéricos
Drugs, Generic
Equivalencia Terapéutica
Therapeutic Equivalency
- Rights
- openAccess
- License
- http://purl.org/coar/access_right/c_abf2
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oai:bibliotecadigital.udea.edu.co:10495/26412 |
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UDEA2 |
network_name_str |
Repositorio UdeA |
repository_id_str |
|
dc.title.spa.fl_str_mv |
Determination of Therapeutic Equivalence (TE) of 5 Generic Products (GP) of Penicillin G (PEN) Using the Neutropenic Murine Thigh Infection Model (NMTIM) |
title |
Determination of Therapeutic Equivalence (TE) of 5 Generic Products (GP) of Penicillin G (PEN) Using the Neutropenic Murine Thigh Infection Model (NMTIM) |
spellingShingle |
Determination of Therapeutic Equivalence (TE) of 5 Generic Products (GP) of Penicillin G (PEN) Using the Neutropenic Murine Thigh Infection Model (NMTIM) Penicilina G Penicillin G Medicamentos Genéricos Drugs, Generic Equivalencia Terapéutica Therapeutic Equivalency |
title_short |
Determination of Therapeutic Equivalence (TE) of 5 Generic Products (GP) of Penicillin G (PEN) Using the Neutropenic Murine Thigh Infection Model (NMTIM) |
title_full |
Determination of Therapeutic Equivalence (TE) of 5 Generic Products (GP) of Penicillin G (PEN) Using the Neutropenic Murine Thigh Infection Model (NMTIM) |
title_fullStr |
Determination of Therapeutic Equivalence (TE) of 5 Generic Products (GP) of Penicillin G (PEN) Using the Neutropenic Murine Thigh Infection Model (NMTIM) |
title_full_unstemmed |
Determination of Therapeutic Equivalence (TE) of 5 Generic Products (GP) of Penicillin G (PEN) Using the Neutropenic Murine Thigh Infection Model (NMTIM) |
title_sort |
Determination of Therapeutic Equivalence (TE) of 5 Generic Products (GP) of Penicillin G (PEN) Using the Neutropenic Murine Thigh Infection Model (NMTIM) |
dc.creator.fl_str_mv |
Zuluaga Salazar, Andrés Felipe Agudelo Pérez, María Salazar Giraldo, Beatriz Rodríguez Jaramillo, Carlos Andrés Vesga Meneses, Omar |
dc.contributor.author.none.fl_str_mv |
Zuluaga Salazar, Andrés Felipe Agudelo Pérez, María Salazar Giraldo, Beatriz Rodríguez Jaramillo, Carlos Andrés Vesga Meneses, Omar |
dc.subject.decs.none.fl_str_mv |
Penicilina G Penicillin G Medicamentos Genéricos Drugs, Generic Equivalencia Terapéutica Therapeutic Equivalency |
topic |
Penicilina G Penicillin G Medicamentos Genéricos Drugs, Generic Equivalencia Terapéutica Therapeutic Equivalency |
description |
ABSTRACT: Background: Legal use of GP in human and veterinary medicine has great impact in price regulation worldwide, but numbers of GP makers are increasing overwhelmingly. Beyond quality problems, concern is growing about the scientific basis of using bioequivalence (BE) as surrogate proof of TE, the accepted dogma. To test it, bactericidal efficacy of GP of PEN made in Colombia was compared in vitro and in vivo against the original compound (OC) in simultaneous experiments, employing the same methods required for new antimicrobials. Methods: Microbiologic assays with S. aureus ATCC 6538p and broth microdilution minimal inhibitory and bactericidal concentrations (MIC/MBC) were used to determine BE by comparison of standard curves (SC) and in vitro activity. The NMTIM used 6 week-old specific pathogen free ICR:CD-1 female mice weighting 25±2 g infected with S. aureus GRP-0057, a PEN-susceptible clinical isolante. The sigmoid dose-response model was applied to calculate by least squares nonlinear regression (NLR) pharmacodynamic parameters (PDP) like Emax and bacteriostatic dose (BD). SC were compared by linear curve fitting analysis (CFA), whole NLR by nonlinear CFA, individual PDP by nonlinear CFA and Wilcoxon-Mann-Whitney test (WMW), MIC/MBC by WMW. Results: All 5 GP were made in Colombia; 1 had greater amounts of PEN (intercept = 0.0052 vs 0.0041 mg/l, P<0.0001), but did not differ in MIC/MBC from the OC. Only 1 of the other 4 GP had lower MIC/MBC, 0.01/0.02 vs 0.07/0.10 mg/l for the OC (P = 0.013). Mice had 104.49-4.74 CFU/thigh (CFU/g) when treated with PEN 0.094-24 mg/kg for 24 hours (24h) divided q1h. At the end of therapy, untreated controls had 107.65-7.83 CFU/g (24h growth = 2.92-3.33 log10 CFU/g). All 5 GP failed TE: Emax = 2.01-3.26 vs 4.87 log10 CFU/g, and BD = 6.94-120.1 vs 1.65 mg/kg/24h for GP and OC respectively (P<0.0005). Conclusions: GP of PEN do not exhibit TE with the OC. Current criteria for BE and TE deserve review. |
publishDate |
2004 |
dc.date.issued.none.fl_str_mv |
2004 |
dc.date.accessioned.none.fl_str_mv |
2022-03-04T23:05:19Z |
dc.date.available.none.fl_str_mv |
2022-03-04T23:05:19Z |
dc.type.spa.fl_str_mv |
info:eu-repo/semantics/article |
dc.type.coarversion.fl_str_mv |
http://purl.org/coar/version/c_970fb48d4fbd8a85 |
dc.type.hasversion.spa.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.coar.spa.fl_str_mv |
http://purl.org/coar/resource_type/c_2df8fbb1 |
dc.type.redcol.spa.fl_str_mv |
https://purl.org/redcol/resource_type/ART |
dc.type.local.spa.fl_str_mv |
Artículo de investigación |
format |
http://purl.org/coar/resource_type/c_2df8fbb1 |
status_str |
publishedVersion |
dc.identifier.issn.none.fl_str_mv |
0733-6373 |
dc.identifier.uri.none.fl_str_mv |
http://hdl.handle.net/10495/26412 |
identifier_str_mv |
0733-6373 |
url |
http://hdl.handle.net/10495/26412 |
dc.language.iso.spa.fl_str_mv |
eng |
language |
eng |
dc.rights.spa.fl_str_mv |
info:eu-repo/semantics/openAccess |
dc.rights.accessrights.spa.fl_str_mv |
http://purl.org/coar/access_right/c_abf2 |
dc.rights.creativecommons.spa.fl_str_mv |
Derechos reservados - Está prohibida la reproducción parcial o total de esta publicación |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
http://purl.org/coar/access_right/c_abf2 Derechos reservados - Está prohibida la reproducción parcial o total de esta publicación |
dc.format.extent.spa.fl_str_mv |
1 |
dc.format.mimetype.spa.fl_str_mv |
application/pdf |
dc.publisher.spa.fl_str_mv |
American Society for Microbiology |
dc.publisher.group.spa.fl_str_mv |
GRIPE: Grupo Investigador de Problemas en Enfermedades Infecciosas |
dc.publisher.place.spa.fl_str_mv |
Washington, Estados Unidos |
institution |
Universidad de Antioquia |
bitstream.url.fl_str_mv |
http://bibliotecadigital.udea.edu.co/bitstream/10495/26412/3/AndresZuluaga_2004_DeterminationPenicillinNneutropenic.pdf http://bibliotecadigital.udea.edu.co/bitstream/10495/26412/2/license.txt |
bitstream.checksum.fl_str_mv |
a4c986a6121fd0aeec48eb2b3ad7d1ec 8a4605be74aa9ea9d79846c1fba20a33 |
bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 |
repository.name.fl_str_mv |
Repositorio Institucional Universidad de Antioquia |
repository.mail.fl_str_mv |
andres.perez@udea.edu.co |
_version_ |
1812173157937709056 |
spelling |
Zuluaga Salazar, Andrés FelipeAgudelo Pérez, MaríaSalazar Giraldo, BeatrizRodríguez Jaramillo, Carlos AndrésVesga Meneses, Omar2022-03-04T23:05:19Z2022-03-04T23:05:19Z20040733-6373http://hdl.handle.net/10495/26412ABSTRACT: Background: Legal use of GP in human and veterinary medicine has great impact in price regulation worldwide, but numbers of GP makers are increasing overwhelmingly. Beyond quality problems, concern is growing about the scientific basis of using bioequivalence (BE) as surrogate proof of TE, the accepted dogma. To test it, bactericidal efficacy of GP of PEN made in Colombia was compared in vitro and in vivo against the original compound (OC) in simultaneous experiments, employing the same methods required for new antimicrobials. Methods: Microbiologic assays with S. aureus ATCC 6538p and broth microdilution minimal inhibitory and bactericidal concentrations (MIC/MBC) were used to determine BE by comparison of standard curves (SC) and in vitro activity. The NMTIM used 6 week-old specific pathogen free ICR:CD-1 female mice weighting 25±2 g infected with S. aureus GRP-0057, a PEN-susceptible clinical isolante. The sigmoid dose-response model was applied to calculate by least squares nonlinear regression (NLR) pharmacodynamic parameters (PDP) like Emax and bacteriostatic dose (BD). SC were compared by linear curve fitting analysis (CFA), whole NLR by nonlinear CFA, individual PDP by nonlinear CFA and Wilcoxon-Mann-Whitney test (WMW), MIC/MBC by WMW. Results: All 5 GP were made in Colombia; 1 had greater amounts of PEN (intercept = 0.0052 vs 0.0041 mg/l, P<0.0001), but did not differ in MIC/MBC from the OC. Only 1 of the other 4 GP had lower MIC/MBC, 0.01/0.02 vs 0.07/0.10 mg/l for the OC (P = 0.013). Mice had 104.49-4.74 CFU/thigh (CFU/g) when treated with PEN 0.094-24 mg/kg for 24 hours (24h) divided q1h. At the end of therapy, untreated controls had 107.65-7.83 CFU/g (24h growth = 2.92-3.33 log10 CFU/g). All 5 GP failed TE: Emax = 2.01-3.26 vs 4.87 log10 CFU/g, and BD = 6.94-120.1 vs 1.65 mg/kg/24h for GP and OC respectively (P<0.0005). Conclusions: GP of PEN do not exhibit TE with the OC. Current criteria for BE and TE deserve review.COL00057441application/pdfengAmerican Society for MicrobiologyGRIPE: Grupo Investigador de Problemas en Enfermedades InfecciosasWashington, Estados Unidosinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_2df8fbb1https://purl.org/redcol/resource_type/ARTArtículo de investigaciónhttp://purl.org/coar/version/c_970fb48d4fbd8a85info:eu-repo/semantics/openAccesshttp://purl.org/coar/access_right/c_abf2Derechos reservados - Está prohibida la reproducción parcial o total de esta publicaciónDetermination of Therapeutic Equivalence (TE) of 5 Generic Products (GP) of Penicillin G (PEN) Using the Neutropenic Murine Thigh Infection Model (NMTIM)Penicilina GPenicillin GMedicamentos GenéricosDrugs, GenericEquivalencia TerapéuticaTherapeutic EquivalencyAbstracts of the Interscience Conference on Antimicrobial Agents and Chemotherapy4040ORIGINALAndresZuluaga_2004_DeterminationPenicillinNneutropenic.pdfAndresZuluaga_2004_DeterminationPenicillinNneutropenic.pdfArtículo de investigaciónapplication/pdf7435432http://bibliotecadigital.udea.edu.co/bitstream/10495/26412/3/AndresZuluaga_2004_DeterminationPenicillinNneutropenic.pdfa4c986a6121fd0aeec48eb2b3ad7d1ecMD53LICENSElicense.txtlicense.txttext/plain; charset=utf-81748http://bibliotecadigital.udea.edu.co/bitstream/10495/26412/2/license.txt8a4605be74aa9ea9d79846c1fba20a33MD5210495/26412oai:bibliotecadigital.udea.edu.co:10495/264122022-03-04 18:07:03.035Repositorio Institucional Universidad de Antioquiaandres.perez@udea.edu.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 |