The ABCG2 efflux transporter in the mammary gland mediates veterinary drug secretion across the blood-milk barrier into milk of dairy cows

Autores
Mahnke, Hanna; Ballent, Mariana; Baumann, Sven; Imperiale, Fernanda Andrea; Von Bergen, Martin; Lanusse, Carlos Edmundo; Lifschitz, Adrian Luis; Honscha, Walther; Halwachs, Sandra
Año de publicación
2016
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
In human and mice ATP-binding cassette efflux transporter ABCG2 represents themain route for active drug transport into milk. However, there is no detailed information on the role of ABCG2 in drug secretion and accumulation in milk of dairy animals. We therefore examined ABCG2-mediated drug transport in the bovine mammary gland by parallel pharmacokinetic studies in lactating Jersey cows and in vitro flux studies using the anthelmintic drug monepantel (MNP) as representative bovine ABCG2 (bABCG2) drug substrate. Animals received MNP (Zolvix, Novartis Animal Health Inc.) once (2.5 mg/kg per os) and the concentrations of MNP and the active MNP metabolite MNPSO2 were assessed by high-performance liquid chromatography. Comparedwith the parent drugMNP,we detected higherMNPSO2 plasma concentrations (expressed as area under the concentration-versustime curve). Moreover, we observed MNPSO2 excretion into milk of dairy cows with a high milk-to-plasmaratio of 6.75. Inmechanistic flux assays, we determined a preferential time-dependent basolateral-toapical (B > A) MNPSO2 transport across polarized Madin-Darby canine kidney II cells-bABCG2 monolayers using liquid chromatography coupled with tandem mass spectrometry analysis. The B > A MNPSO2 transport was significantly inhibited by the ABCG2 inhibitor fumitremorgin C in bABCG2- but not in mock-transduced MDCKII cells. Additionally, the antibiotic drug enrofloxacin, the benzimidazole anthelmintic oxfendazole and the macrocyclic lactone anthelmintic moxidectin caused a reduction in the MNPSO2 (B > A) net efflux. Altogether, this study indicated that therapeutically relevant drugs like the anthelminticMNP represent substrates of the bovine mammary ABCG2 transporter and may thereby be actively concentrated in dairy milk.
Fil: Mahnke, Hanna. University of Leipzig; Alemania
Fil: Ballent, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Baumann, Sven. University of Leipzig; Alemania. Helmholtz Centre for Environmental Research; Alemania
Fil: Imperiale, Fernanda Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Von Bergen, Martin. Helmholtz Centre for Environmental Research; Alemania. Aalborg University; Dinamarca
Fil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Honscha, Walther. University of Leipzig; Alemania
Fil: Halwachs, Sandra. University of Leipzig; Alemania
Materia
Abcg2
Mammary Gland
Blood-Brain Barrier
Dairy Cows
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:11336/58584
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/58584
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling The ABCG2 efflux transporter in the mammary gland mediates veterinary drug secretion across the blood-milk barrier into milk of dairy cowsMahnke, HannaBallent, MarianaBaumann, SvenImperiale, Fernanda AndreaVon Bergen, MartinLanusse, Carlos EdmundoLifschitz, Adrian LuisHonscha, WaltherHalwachs, SandraAbcg2Mammary GlandBlood-Brain BarrierDairy Cowshttps://purl.org/becyt/ford/4.3https://purl.org/becyt/ford/4In human and mice ATP-binding cassette efflux transporter ABCG2 represents themain route for active drug transport into milk. However, there is no detailed information on the role of ABCG2 in drug secretion and accumulation in milk of dairy animals. We therefore examined ABCG2-mediated drug transport in the bovine mammary gland by parallel pharmacokinetic studies in lactating Jersey cows and in vitro flux studies using the anthelmintic drug monepantel (MNP) as representative bovine ABCG2 (bABCG2) drug substrate. Animals received MNP (Zolvix, Novartis Animal Health Inc.) once (2.5 mg/kg per os) and the concentrations of MNP and the active MNP metabolite MNPSO2 were assessed by high-performance liquid chromatography. Comparedwith the parent drugMNP,we detected higherMNPSO2 plasma concentrations (expressed as area under the concentration-versustime curve). Moreover, we observed MNPSO2 excretion into milk of dairy cows with a high milk-to-plasmaratio of 6.75. Inmechanistic flux assays, we determined a preferential time-dependent basolateral-toapical (B > A) MNPSO2 transport across polarized Madin-Darby canine kidney II cells-bABCG2 monolayers using liquid chromatography coupled with tandem mass spectrometry analysis. The B > A MNPSO2 transport was significantly inhibited by the ABCG2 inhibitor fumitremorgin C in bABCG2- but not in mock-transduced MDCKII cells. Additionally, the antibiotic drug enrofloxacin, the benzimidazole anthelmintic oxfendazole and the macrocyclic lactone anthelmintic moxidectin caused a reduction in the MNPSO2 (B > A) net efflux. Altogether, this study indicated that therapeutically relevant drugs like the anthelminticMNP represent substrates of the bovine mammary ABCG2 transporter and may thereby be actively concentrated in dairy milk.Fil: Mahnke, Hanna. University of Leipzig; AlemaniaFil: Ballent, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Baumann, Sven. University of Leipzig; Alemania. Helmholtz Centre for Environmental Research; AlemaniaFil: Imperiale, Fernanda Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Von Bergen, Martin. Helmholtz Centre for Environmental Research; Alemania. Aalborg University; DinamarcaFil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; ArgentinaFil: Honscha, Walther. University of Leipzig; AlemaniaFil: Halwachs, Sandra. University of Leipzig; AlemaniaAmerican Society for Pharmacology and Experimental Therapeutics2016-05info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/58584Mahnke, Hanna; Ballent, Mariana; Baumann, Sven; Imperiale, Fernanda Andrea; Von Bergen, Martin; et al.; The ABCG2 efflux transporter in the mammary gland mediates veterinary drug secretion across the blood-milk barrier into milk of dairy cows; American Society for Pharmacology and Experimental Therapeutics; Drug Metabolism and Disposition; 44; 5; 5-2016; 700-7080090-9556CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1124/dmd.115.068940info:eu-repo/semantics/altIdentifier/url/http://dmd.aspetjournals.org/content/44/5/700.longinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:12:52Zoai:ri.conicet.gov.ar:11336/58584instacron: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:34982025-09-10 13:12:53.054CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv The ABCG2 efflux transporter in the mammary gland mediates veterinary drug secretion across the blood-milk barrier into milk of dairy cows
title The ABCG2 efflux transporter in the mammary gland mediates veterinary drug secretion across the blood-milk barrier into milk of dairy cows
spellingShingle The ABCG2 efflux transporter in the mammary gland mediates veterinary drug secretion across the blood-milk barrier into milk of dairy cows
Mahnke, Hanna
Abcg2
Mammary Gland
Blood-Brain Barrier
Dairy Cows
title_short The ABCG2 efflux transporter in the mammary gland mediates veterinary drug secretion across the blood-milk barrier into milk of dairy cows
title_full The ABCG2 efflux transporter in the mammary gland mediates veterinary drug secretion across the blood-milk barrier into milk of dairy cows
title_fullStr The ABCG2 efflux transporter in the mammary gland mediates veterinary drug secretion across the blood-milk barrier into milk of dairy cows
title_full_unstemmed The ABCG2 efflux transporter in the mammary gland mediates veterinary drug secretion across the blood-milk barrier into milk of dairy cows
title_sort The ABCG2 efflux transporter in the mammary gland mediates veterinary drug secretion across the blood-milk barrier into milk of dairy cows
dc.creator.none.fl_str_mv Mahnke, Hanna
Ballent, Mariana
Baumann, Sven
Imperiale, Fernanda Andrea
Von Bergen, Martin
Lanusse, Carlos Edmundo
Lifschitz, Adrian Luis
Honscha, Walther
Halwachs, Sandra
author Mahnke, Hanna
author_facet Mahnke, Hanna
Ballent, Mariana
Baumann, Sven
Imperiale, Fernanda Andrea
Von Bergen, Martin
Lanusse, Carlos Edmundo
Lifschitz, Adrian Luis
Honscha, Walther
Halwachs, Sandra
author_role author
author2 Ballent, Mariana
Baumann, Sven
Imperiale, Fernanda Andrea
Von Bergen, Martin
Lanusse, Carlos Edmundo
Lifschitz, Adrian Luis
Honscha, Walther
Halwachs, Sandra
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Abcg2
Mammary Gland
Blood-Brain Barrier
Dairy Cows
topic Abcg2
Mammary Gland
Blood-Brain Barrier
Dairy Cows
purl_subject.fl_str_mv https://purl.org/becyt/ford/4.3
https://purl.org/becyt/ford/4
dc.description.none.fl_txt_mv In human and mice ATP-binding cassette efflux transporter ABCG2 represents themain route for active drug transport into milk. However, there is no detailed information on the role of ABCG2 in drug secretion and accumulation in milk of dairy animals. We therefore examined ABCG2-mediated drug transport in the bovine mammary gland by parallel pharmacokinetic studies in lactating Jersey cows and in vitro flux studies using the anthelmintic drug monepantel (MNP) as representative bovine ABCG2 (bABCG2) drug substrate. Animals received MNP (Zolvix, Novartis Animal Health Inc.) once (2.5 mg/kg per os) and the concentrations of MNP and the active MNP metabolite MNPSO2 were assessed by high-performance liquid chromatography. Comparedwith the parent drugMNP,we detected higherMNPSO2 plasma concentrations (expressed as area under the concentration-versustime curve). Moreover, we observed MNPSO2 excretion into milk of dairy cows with a high milk-to-plasmaratio of 6.75. Inmechanistic flux assays, we determined a preferential time-dependent basolateral-toapical (B > A) MNPSO2 transport across polarized Madin-Darby canine kidney II cells-bABCG2 monolayers using liquid chromatography coupled with tandem mass spectrometry analysis. The B > A MNPSO2 transport was significantly inhibited by the ABCG2 inhibitor fumitremorgin C in bABCG2- but not in mock-transduced MDCKII cells. Additionally, the antibiotic drug enrofloxacin, the benzimidazole anthelmintic oxfendazole and the macrocyclic lactone anthelmintic moxidectin caused a reduction in the MNPSO2 (B > A) net efflux. Altogether, this study indicated that therapeutically relevant drugs like the anthelminticMNP represent substrates of the bovine mammary ABCG2 transporter and may thereby be actively concentrated in dairy milk.
Fil: Mahnke, Hanna. University of Leipzig; Alemania
Fil: Ballent, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Baumann, Sven. University of Leipzig; Alemania. Helmholtz Centre for Environmental Research; Alemania
Fil: Imperiale, Fernanda Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Von Bergen, Martin. Helmholtz Centre for Environmental Research; Alemania. Aalborg University; Dinamarca
Fil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina
Fil: Honscha, Walther. University of Leipzig; Alemania
Fil: Halwachs, Sandra. University of Leipzig; Alemania
description In human and mice ATP-binding cassette efflux transporter ABCG2 represents themain route for active drug transport into milk. However, there is no detailed information on the role of ABCG2 in drug secretion and accumulation in milk of dairy animals. We therefore examined ABCG2-mediated drug transport in the bovine mammary gland by parallel pharmacokinetic studies in lactating Jersey cows and in vitro flux studies using the anthelmintic drug monepantel (MNP) as representative bovine ABCG2 (bABCG2) drug substrate. Animals received MNP (Zolvix, Novartis Animal Health Inc.) once (2.5 mg/kg per os) and the concentrations of MNP and the active MNP metabolite MNPSO2 were assessed by high-performance liquid chromatography. Comparedwith the parent drugMNP,we detected higherMNPSO2 plasma concentrations (expressed as area under the concentration-versustime curve). Moreover, we observed MNPSO2 excretion into milk of dairy cows with a high milk-to-plasmaratio of 6.75. Inmechanistic flux assays, we determined a preferential time-dependent basolateral-toapical (B > A) MNPSO2 transport across polarized Madin-Darby canine kidney II cells-bABCG2 monolayers using liquid chromatography coupled with tandem mass spectrometry analysis. The B > A MNPSO2 transport was significantly inhibited by the ABCG2 inhibitor fumitremorgin C in bABCG2- but not in mock-transduced MDCKII cells. Additionally, the antibiotic drug enrofloxacin, the benzimidazole anthelmintic oxfendazole and the macrocyclic lactone anthelmintic moxidectin caused a reduction in the MNPSO2 (B > A) net efflux. Altogether, this study indicated that therapeutically relevant drugs like the anthelminticMNP represent substrates of the bovine mammary ABCG2 transporter and may thereby be actively concentrated in dairy milk.
publishDate 2016
dc.date.none.fl_str_mv 2016-05
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/11336/58584
Mahnke, Hanna; Ballent, Mariana; Baumann, Sven; Imperiale, Fernanda Andrea; Von Bergen, Martin; et al.; The ABCG2 efflux transporter in the mammary gland mediates veterinary drug secretion across the blood-milk barrier into milk of dairy cows; American Society for Pharmacology and Experimental Therapeutics; Drug Metabolism and Disposition; 44; 5; 5-2016; 700-708
0090-9556
CONICET Digital
CONICET
url http://hdl.handle.net/11336/58584
identifier_str_mv Mahnke, Hanna; Ballent, Mariana; Baumann, Sven; Imperiale, Fernanda Andrea; Von Bergen, Martin; et al.; The ABCG2 efflux transporter in the mammary gland mediates veterinary drug secretion across the blood-milk barrier into milk of dairy cows; American Society for Pharmacology and Experimental Therapeutics; Drug Metabolism and Disposition; 44; 5; 5-2016; 700-708
0090-9556
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
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info:eu-repo/semantics/altIdentifier/url/http://dmd.aspetjournals.org/content/44/5/700.long
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
application/pdf
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dc.publisher.none.fl_str_mv American Society for Pharmacology and Experimental Therapeutics
publisher.none.fl_str_mv American Society for Pharmacology and Experimental Therapeutics
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
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