Role of the Abcg2 Transporter in Secretion into Milk of the Anthelmintic Clorsulon: Interaction with Ivermectin

[EN] Clorsulon is a benzenesulfonamide drug that is effective in treating helminthic zoonoses such as fascioliasis. When used in combination with the macrocyclic lactone ivermectin, it provides high broad-spectrum antiparasitic efficacy. The safety and efficacy of clorsulon should be studied by cons...

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Autores: Blanco Paniagua, Esther, Álvarez Fernández, Laura, Rodríguez Alonso, Andrea, Millán García, Alicia, Álvarez de Felipe, Ana Isabel, Merino Peláez, Gracia
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2023
País:España
Institución:Ajuntament de Barcelona
Repositorio:BULERIA. Repositorio Institucional de la Universidad de León
OAI Identifier:oai:buleria.unileon.es:10612/17411
Acceso en línea:https://hdl.handle.net/10612/17411
Access Level:acceso abierto
Palabra clave:Fisiología
ABCG2
Clorsulon
Substrate
Milk
Ivermectin
ABC transporters
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spelling Role of the Abcg2 Transporter in Secretion into Milk of the Anthelmintic Clorsulon: Interaction with IvermectinBlanco Paniagua, EstherÁlvarez Fernández, LauraRodríguez Alonso, AndreaMillán García, AliciaÁlvarez de Felipe, Ana IsabelMerino Peláez, GraciaFisiologíaABCG2ClorsulonSubstrateMilkIvermectinABC transporters[EN] Clorsulon is a benzenesulfonamide drug that is effective in treating helminthic zoonoses such as fascioliasis. When used in combination with the macrocyclic lactone ivermectin, it provides high broad-spectrum antiparasitic efficacy. The safety and efficacy of clorsulon should be studied by considering several factors such as drug-drug interactions mediated by ATP-binding cassette (ABC) transporters due to their potential effects on the pharmacokinetics and drug secretion into milk. The aim of this work was to determine the role of ABC transporter G2 (ABCG2) in clorsulon secretion into milk and the effect of ivermectin, a known ABCG2 inhibitor, on this process. Using in vitro transepithelial assays with cells transduced with murine Abcg2 and human ABCG2, we report that clorsulon was transported in vitro by both transporter variants and that ivermectin inhibited its transport mediated by murine Abcg2 and human ABCG2. Wild-type and Abcg22/2 lactating female mice were used to carry out in vivo assays. The milk concentration and the milk-to-plasma ratio were higher in wild-type mice than in Abcg22/2 mice after clorsulon administration, showing that clorsulon is actively secreted into milk by Abcg2. The interaction of ivermectin in this process was shown after the coadministration of clorsulon and ivermectin to wild-type and Abcg22/2 lactating female mice. Treatment with ivermectin had no effect on the plasma concentrations of clorsulon, but the milk concentrations and milk-to-plasma ratios of clorsulon decreased in comparison to those with treatment without ivermectin, only in wild-type animals. Consequently, the coadministration of clorsulon and ivermectin reduces clorsulon secretion into milk due to drug-drug interactions mediated by ABCG2SIAmerican Society for MicrobiologyFisiologiaFacultad de Veterinaria2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/acceptedVersionhttps://hdl.handle.net/10612/17411reponame:BULERIA. Repositorio Institucional de la Universidad de Leóninstname:Ajuntament de BarcelonaIngléshttps://journals.asm.org/doi/10.1128/aac.00095-23http://creativecommons.org/licenses/by/4.0/info:eu-repo/semantics/openAccessoai:buleria.unileon.es:10612/174112026-06-24T12:43:27Z
dc.title.none.fl_str_mv Role of the Abcg2 Transporter in Secretion into Milk of the Anthelmintic Clorsulon: Interaction with Ivermectin
title Role of the Abcg2 Transporter in Secretion into Milk of the Anthelmintic Clorsulon: Interaction with Ivermectin
spellingShingle Role of the Abcg2 Transporter in Secretion into Milk of the Anthelmintic Clorsulon: Interaction with Ivermectin
Blanco Paniagua, Esther
Fisiología
ABCG2
Clorsulon
Substrate
Milk
Ivermectin
ABC transporters
title_short Role of the Abcg2 Transporter in Secretion into Milk of the Anthelmintic Clorsulon: Interaction with Ivermectin
title_full Role of the Abcg2 Transporter in Secretion into Milk of the Anthelmintic Clorsulon: Interaction with Ivermectin
title_fullStr Role of the Abcg2 Transporter in Secretion into Milk of the Anthelmintic Clorsulon: Interaction with Ivermectin
title_full_unstemmed Role of the Abcg2 Transporter in Secretion into Milk of the Anthelmintic Clorsulon: Interaction with Ivermectin
title_sort Role of the Abcg2 Transporter in Secretion into Milk of the Anthelmintic Clorsulon: Interaction with Ivermectin
dc.creator.none.fl_str_mv Blanco Paniagua, Esther
Álvarez Fernández, Laura
Rodríguez Alonso, Andrea
Millán García, Alicia
Álvarez de Felipe, Ana Isabel
Merino Peláez, Gracia
author Blanco Paniagua, Esther
author_facet Blanco Paniagua, Esther
Álvarez Fernández, Laura
Rodríguez Alonso, Andrea
Millán García, Alicia
Álvarez de Felipe, Ana Isabel
Merino Peláez, Gracia
author_role author
author2 Álvarez Fernández, Laura
Rodríguez Alonso, Andrea
Millán García, Alicia
Álvarez de Felipe, Ana Isabel
Merino Peláez, Gracia
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Fisiologia
Facultad de Veterinaria
dc.subject.none.fl_str_mv Fisiología
ABCG2
Clorsulon
Substrate
Milk
Ivermectin
ABC transporters
topic Fisiología
ABCG2
Clorsulon
Substrate
Milk
Ivermectin
ABC transporters
description [EN] Clorsulon is a benzenesulfonamide drug that is effective in treating helminthic zoonoses such as fascioliasis. When used in combination with the macrocyclic lactone ivermectin, it provides high broad-spectrum antiparasitic efficacy. The safety and efficacy of clorsulon should be studied by considering several factors such as drug-drug interactions mediated by ATP-binding cassette (ABC) transporters due to their potential effects on the pharmacokinetics and drug secretion into milk. The aim of this work was to determine the role of ABC transporter G2 (ABCG2) in clorsulon secretion into milk and the effect of ivermectin, a known ABCG2 inhibitor, on this process. Using in vitro transepithelial assays with cells transduced with murine Abcg2 and human ABCG2, we report that clorsulon was transported in vitro by both transporter variants and that ivermectin inhibited its transport mediated by murine Abcg2 and human ABCG2. Wild-type and Abcg22/2 lactating female mice were used to carry out in vivo assays. The milk concentration and the milk-to-plasma ratio were higher in wild-type mice than in Abcg22/2 mice after clorsulon administration, showing that clorsulon is actively secreted into milk by Abcg2. The interaction of ivermectin in this process was shown after the coadministration of clorsulon and ivermectin to wild-type and Abcg22/2 lactating female mice. Treatment with ivermectin had no effect on the plasma concentrations of clorsulon, but the milk concentrations and milk-to-plasma ratios of clorsulon decreased in comparison to those with treatment without ivermectin, only in wild-type animals. Consequently, the coadministration of clorsulon and ivermectin reduces clorsulon secretion into milk due to drug-drug interactions mediated by ABCG2
publishDate 2023
dc.date.none.fl_str_mv 2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/acceptedVersion
format article
status_str acceptedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/10612/17411
url https://hdl.handle.net/10612/17411
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv https://journals.asm.org/doi/10.1128/aac.00095-23
dc.rights.none.fl_str_mv http://creativecommons.org/licenses/by/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:BULERIA. Repositorio Institucional de la Universidad de León
instname:Ajuntament de Barcelona
instname_str Ajuntament de Barcelona
reponame_str BULERIA. Repositorio Institucional de la Universidad de León
collection BULERIA. Repositorio Institucional de la Universidad de León
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869412474007060480
score 15.300719

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