Cardiovascular, liver, and renal toxicity associated with an intravenous ferric carboxymaltose similar versus the originator compound

Autores
Toblli, Jorge Eduardo; Cao, Gabriel Fernando; Rico, Luis; Angerosa, Margarita
Año de publicación
2017
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Background: Ferric carboxymaltose (FCM) is a stable, non-dextran-based intravenous iron complex used to treat iron deficiency of various etiologies. As FCM is a nonbiological complex drug and cannot be fully characterized by physicochemical analyses, it is important to demonstrate in nonclinical models that FCM similars (FCMS) have similar biodistribution. Materials and methods: A total of 30 nonanemic rats were treated weekly with 40 mg iron/kg body weight intravenous FCM, FCMS, or isotonic saline (controls) for 4 weeks. Blood pressure, liver enzymes, and renal function were evaluated. In liver, heart, and kidney tissue, markers for oxidative stress (malondialdehyde to assess lipid peroxidation and antioxidant enzymes) and inflammation (TNFα and IL6) were measured. Iron deposits were localized. Results: The FCMS-treated group had significantly lower blood pressure, higher liver enzymes, increased proteinuria, and reduced creatinine clearance versus the FCM and control groups by day 29. Serum iron and transferrin saturation were significantly higher with FCMS versus FCM or controls. Iron deposition was altered in FCMS-treated animals, with decreased ferritin deposits and iron deposition outside the physiological storage compartments. Markers for lipid peroxidation and antioxidant-enzyme activity were significantly increased after FCMS administration versus FCM and controls, as were inflammatory markers. Conclusion: Results from this blinded nonclinical study demonstrated significant differences between the originator FCM and this FCMS.
Fil: Toblli, Jorge Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán; Argentina. Universidad de Buenos Aires; Argentina
Fil: Cao, Gabriel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán; Argentina. Universidad de Buenos Aires; Argentina
Fil: Rico, Luis. Hospital Alemán; Argentina. Universidad de Buenos Aires; Argentina
Fil: Angerosa, Margarita. Hospital Alemán; Argentina. Universidad de Buenos Aires; Argentina
Materia
Ferinject
Ferric Carboxymaltose
Follow-Ons
Nonbiological Complex Drugs
Orofer
Oxidative Stress
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/66709
Acceder
id CONICETDig_7999fec2c1f99a9f30c969a69344a96c
oai_identifier_str oai:ri.conicet.gov.ar:11336/66709
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Cardiovascular, liver, and renal toxicity associated with an intravenous ferric carboxymaltose similar versus the originator compoundToblli, Jorge EduardoCao, Gabriel FernandoRico, LuisAngerosa, MargaritaFerinjectFerric CarboxymaltoseFollow-OnsNonbiological Complex DrugsOroferOxidative Stresshttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Background: Ferric carboxymaltose (FCM) is a stable, non-dextran-based intravenous iron complex used to treat iron deficiency of various etiologies. As FCM is a nonbiological complex drug and cannot be fully characterized by physicochemical analyses, it is important to demonstrate in nonclinical models that FCM similars (FCMS) have similar biodistribution. Materials and methods: A total of 30 nonanemic rats were treated weekly with 40 mg iron/kg body weight intravenous FCM, FCMS, or isotonic saline (controls) for 4 weeks. Blood pressure, liver enzymes, and renal function were evaluated. In liver, heart, and kidney tissue, markers for oxidative stress (malondialdehyde to assess lipid peroxidation and antioxidant enzymes) and inflammation (TNFα and IL6) were measured. Iron deposits were localized. Results: The FCMS-treated group had significantly lower blood pressure, higher liver enzymes, increased proteinuria, and reduced creatinine clearance versus the FCM and control groups by day 29. Serum iron and transferrin saturation were significantly higher with FCMS versus FCM or controls. Iron deposition was altered in FCMS-treated animals, with decreased ferritin deposits and iron deposition outside the physiological storage compartments. Markers for lipid peroxidation and antioxidant-enzyme activity were significantly increased after FCMS administration versus FCM and controls, as were inflammatory markers. Conclusion: Results from this blinded nonclinical study demonstrated significant differences between the originator FCM and this FCMS.Fil: Toblli, Jorge Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán; Argentina. Universidad de Buenos Aires; ArgentinaFil: Cao, Gabriel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán; Argentina. Universidad de Buenos Aires; ArgentinaFil: Rico, Luis. Hospital Alemán; Argentina. Universidad de Buenos Aires; ArgentinaFil: Angerosa, Margarita. Hospital Alemán; Argentina. Universidad de Buenos Aires; ArgentinaDove Medical Press Ltd.2017-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/66709Toblli, Jorge Eduardo; Cao, Gabriel Fernando; Rico, Luis; Angerosa, Margarita; Cardiovascular, liver, and renal toxicity associated with an intravenous ferric carboxymaltose similar versus the originator compound; Dove Medical Press Ltd.; Drug Design, Development and Therapy; 11; 11-2017; 3401-34121177-8881CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.2147/DDDT.S151162info:eu-repo/semantics/altIdentifier/url/https://www.dovepress.com/cardiovascular-liver-and-renal-toxicity-associated-with-an-intravenous-peer-reviewed-article-DDDTinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:51:50Zoai:ri.conicet.gov.ar:11336/66709instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-03 09:51:51.104CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Cardiovascular, liver, and renal toxicity associated with an intravenous ferric carboxymaltose similar versus the originator compound
title Cardiovascular, liver, and renal toxicity associated with an intravenous ferric carboxymaltose similar versus the originator compound
spellingShingle Cardiovascular, liver, and renal toxicity associated with an intravenous ferric carboxymaltose similar versus the originator compound
Toblli, Jorge Eduardo
Ferinject
Ferric Carboxymaltose
Follow-Ons
Nonbiological Complex Drugs
Orofer
Oxidative Stress
title_short Cardiovascular, liver, and renal toxicity associated with an intravenous ferric carboxymaltose similar versus the originator compound
title_full Cardiovascular, liver, and renal toxicity associated with an intravenous ferric carboxymaltose similar versus the originator compound
title_fullStr Cardiovascular, liver, and renal toxicity associated with an intravenous ferric carboxymaltose similar versus the originator compound
title_full_unstemmed Cardiovascular, liver, and renal toxicity associated with an intravenous ferric carboxymaltose similar versus the originator compound
title_sort Cardiovascular, liver, and renal toxicity associated with an intravenous ferric carboxymaltose similar versus the originator compound
dc.creator.none.fl_str_mv Toblli, Jorge Eduardo
Cao, Gabriel Fernando
Rico, Luis
Angerosa, Margarita
author Toblli, Jorge Eduardo
author_facet Toblli, Jorge Eduardo
Cao, Gabriel Fernando
Rico, Luis
Angerosa, Margarita
author_role author
author2 Cao, Gabriel Fernando
Rico, Luis
Angerosa, Margarita
author2_role author
author
author
dc.subject.none.fl_str_mv Ferinject
Ferric Carboxymaltose
Follow-Ons
Nonbiological Complex Drugs
Orofer
Oxidative Stress
topic Ferinject
Ferric Carboxymaltose
Follow-Ons
Nonbiological Complex Drugs
Orofer
Oxidative Stress
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Background: Ferric carboxymaltose (FCM) is a stable, non-dextran-based intravenous iron complex used to treat iron deficiency of various etiologies. As FCM is a nonbiological complex drug and cannot be fully characterized by physicochemical analyses, it is important to demonstrate in nonclinical models that FCM similars (FCMS) have similar biodistribution. Materials and methods: A total of 30 nonanemic rats were treated weekly with 40 mg iron/kg body weight intravenous FCM, FCMS, or isotonic saline (controls) for 4 weeks. Blood pressure, liver enzymes, and renal function were evaluated. In liver, heart, and kidney tissue, markers for oxidative stress (malondialdehyde to assess lipid peroxidation and antioxidant enzymes) and inflammation (TNFα and IL6) were measured. Iron deposits were localized. Results: The FCMS-treated group had significantly lower blood pressure, higher liver enzymes, increased proteinuria, and reduced creatinine clearance versus the FCM and control groups by day 29. Serum iron and transferrin saturation were significantly higher with FCMS versus FCM or controls. Iron deposition was altered in FCMS-treated animals, with decreased ferritin deposits and iron deposition outside the physiological storage compartments. Markers for lipid peroxidation and antioxidant-enzyme activity were significantly increased after FCMS administration versus FCM and controls, as were inflammatory markers. Conclusion: Results from this blinded nonclinical study demonstrated significant differences between the originator FCM and this FCMS.
Fil: Toblli, Jorge Eduardo. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán; Argentina. Universidad de Buenos Aires; Argentina
Fil: Cao, Gabriel Fernando. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Hospital Alemán; Argentina. Universidad de Buenos Aires; Argentina
Fil: Rico, Luis. Hospital Alemán; Argentina. Universidad de Buenos Aires; Argentina
Fil: Angerosa, Margarita. Hospital Alemán; Argentina. Universidad de Buenos Aires; Argentina
description Background: Ferric carboxymaltose (FCM) is a stable, non-dextran-based intravenous iron complex used to treat iron deficiency of various etiologies. As FCM is a nonbiological complex drug and cannot be fully characterized by physicochemical analyses, it is important to demonstrate in nonclinical models that FCM similars (FCMS) have similar biodistribution. Materials and methods: A total of 30 nonanemic rats were treated weekly with 40 mg iron/kg body weight intravenous FCM, FCMS, or isotonic saline (controls) for 4 weeks. Blood pressure, liver enzymes, and renal function were evaluated. In liver, heart, and kidney tissue, markers for oxidative stress (malondialdehyde to assess lipid peroxidation and antioxidant enzymes) and inflammation (TNFα and IL6) were measured. Iron deposits were localized. Results: The FCMS-treated group had significantly lower blood pressure, higher liver enzymes, increased proteinuria, and reduced creatinine clearance versus the FCM and control groups by day 29. Serum iron and transferrin saturation were significantly higher with FCMS versus FCM or controls. Iron deposition was altered in FCMS-treated animals, with decreased ferritin deposits and iron deposition outside the physiological storage compartments. Markers for lipid peroxidation and antioxidant-enzyme activity were significantly increased after FCMS administration versus FCM and controls, as were inflammatory markers. Conclusion: Results from this blinded nonclinical study demonstrated significant differences between the originator FCM and this FCMS.
publishDate 2017
dc.date.none.fl_str_mv 2017-11
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/66709
Toblli, Jorge Eduardo; Cao, Gabriel Fernando; Rico, Luis; Angerosa, Margarita; Cardiovascular, liver, and renal toxicity associated with an intravenous ferric carboxymaltose similar versus the originator compound; Dove Medical Press Ltd.; Drug Design, Development and Therapy; 11; 11-2017; 3401-3412
1177-8881
CONICET Digital
CONICET
url http://hdl.handle.net/11336/66709
identifier_str_mv Toblli, Jorge Eduardo; Cao, Gabriel Fernando; Rico, Luis; Angerosa, Margarita; Cardiovascular, liver, and renal toxicity associated with an intravenous ferric carboxymaltose similar versus the originator compound; Dove Medical Press Ltd.; Drug Design, Development and Therapy; 11; 11-2017; 3401-3412
1177-8881
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.2147/DDDT.S151162
info:eu-repo/semantics/altIdentifier/url/https://www.dovepress.com/cardiovascular-liver-and-renal-toxicity-associated-with-an-intravenous-peer-reviewed-article-DDDT
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Dove Medical Press Ltd.
publisher.none.fl_str_mv Dove Medical Press Ltd.
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1842269120666533888
score 13.13397

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