Interference with P-glycoprotein improves ivermectin activity against adult resistant nematodes in sheep

Autores
Lifschitz, Adrian Luis; Entrocasso, Carlos M.; Alvarez, Luis Ignacio; Lloberas, Maria Mercedes; Ballent, Mariana; Manazza, Gustavo Oscar; Virkel, Guillermo Leon; Borda, Bernardino; Lanusse, Carlos Edmundo
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The in vivo co-administration of ivermectin (IVM) with P-glycoprotein (P-gp) modulator agents has been shown to enhance its systemic availability. However, there is no sufficient evidence on the impact that this type of drug?drug interaction may have on the in vivo efficacy against resistant nematodes in ruminant species. The current work reports on the effects of loperamide (LPM), a P-gp modulating agent, on both IVM kinetic behaviour and anthelmintic activity in infected lambs. Eighteen (18) lambs naturally infected with IVM-resistant gastrointestinal nematodes were allocated into three (3) experimental groups. Group A remained as untreated control. Animals in Groups B and C received IVM (200 μg/kg, subcutaneously) either alone or co-administered with LPM (0.2 mg/kg, twice every 12 h), respectively. Individual faecal samples were collected from experimental animals at days −1 and 14 post-treatment to perform the faecal eggs count reduction test (FECRT). Blood samples were collected between 0 and 14 days post-treatment and IVM plasma concentrations were determined by HPLC. Additionally, at day 14 post-treatment, lambs from all experimental groups were sacrificed and adult gastrointestinal nematode counts were performed. FECRT values increased from 78.6 (IVM alone) to 96% (IVM + LPM). Haemonchus contortus was highly resistant to IVM. The IVM alone treatment was completely ineffective (0% efficacy) against adult H. contortus. This efficacy value increased up to 72.5% in the presence of LPM. The efficacy against Trichostrongylus colubriformis increased from 77.9% (IVM alone) to 96.3% (IVM + LPM). The described favorable tendency towards improved anthelmintic efficacy was in agreement with the enhanced IVM plasma availability (P < 0.05) and prolonged elimination half-life (P < 0.05) induced by LPM in infected lambs. A LPM-induced P-gp modulation increases IVM systemic exposure in the host but also it may reduce P-gp efflux transport over-expressed in target resistant nematodes
Fil: Lifschitz, Adrian Luis. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Entrocasso, Carlos M.. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Agencia de Extensión Rural Balcarce; Argentina
Fil: Alvarez, Luis Ignacio. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Lloberas, Maria Mercedes. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Agencia de Extensión Rural Balcarce; Argentina
Fil: Ballent, Mariana. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Manazza, Gustavo Oscar. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Agencia de Extensión Rural Balcarce; Argentina
Fil: Virkel, Guillermo Leon. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Borda, Bernardino. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Agencia de Extensión Rural Balcarce; Argentina
Fil: Lanusse, Carlos Edmundo. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Materia
IVERMECTIN
SHEEP
RESISTANCE NEMATODES
PHARMACOKINETICS
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:11336/112499
Acceder
id CONICETDig_037d8a6ab9967cab3a36994f01fa527d
oai_identifier_str oai:ri.conicet.gov.ar:11336/112499
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Interference with P-glycoprotein improves ivermectin activity against adult resistant nematodes in sheepLifschitz, Adrian LuisEntrocasso, Carlos M.Alvarez, Luis IgnacioLloberas, Maria MercedesBallent, MarianaManazza, Gustavo OscarVirkel, Guillermo LeonBorda, BernardinoLanusse, Carlos EdmundoIVERMECTINSHEEPRESISTANCE NEMATODESPHARMACOKINETICShttps://purl.org/becyt/ford/4.3https://purl.org/becyt/ford/4The in vivo co-administration of ivermectin (IVM) with P-glycoprotein (P-gp) modulator agents has been shown to enhance its systemic availability. However, there is no sufficient evidence on the impact that this type of drug?drug interaction may have on the in vivo efficacy against resistant nematodes in ruminant species. The current work reports on the effects of loperamide (LPM), a P-gp modulating agent, on both IVM kinetic behaviour and anthelmintic activity in infected lambs. Eighteen (18) lambs naturally infected with IVM-resistant gastrointestinal nematodes were allocated into three (3) experimental groups. Group A remained as untreated control. Animals in Groups B and C received IVM (200 μg/kg, subcutaneously) either alone or co-administered with LPM (0.2 mg/kg, twice every 12 h), respectively. Individual faecal samples were collected from experimental animals at days −1 and 14 post-treatment to perform the faecal eggs count reduction test (FECRT). Blood samples were collected between 0 and 14 days post-treatment and IVM plasma concentrations were determined by HPLC. Additionally, at day 14 post-treatment, lambs from all experimental groups were sacrificed and adult gastrointestinal nematode counts were performed. FECRT values increased from 78.6 (IVM alone) to 96% (IVM + LPM). Haemonchus contortus was highly resistant to IVM. The IVM alone treatment was completely ineffective (0% efficacy) against adult H. contortus. This efficacy value increased up to 72.5% in the presence of LPM. The efficacy against Trichostrongylus colubriformis increased from 77.9% (IVM alone) to 96.3% (IVM + LPM). The described favorable tendency towards improved anthelmintic efficacy was in agreement with the enhanced IVM plasma availability (P < 0.05) and prolonged elimination half-life (P < 0.05) induced by LPM in infected lambs. A LPM-induced P-gp modulation increases IVM systemic exposure in the host but also it may reduce P-gp efflux transport over-expressed in target resistant nematodesFil: Lifschitz, Adrian Luis. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Entrocasso, Carlos M.. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Agencia de Extensión Rural Balcarce; ArgentinaFil: Alvarez, Luis Ignacio. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Lloberas, Maria Mercedes. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Agencia de Extensión Rural Balcarce; ArgentinaFil: Ballent, Mariana. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Manazza, Gustavo Oscar. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Agencia de Extensión Rural Balcarce; ArgentinaFil: Virkel, Guillermo Leon. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Borda, Bernardino. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Agencia de Extensión Rural Balcarce; ArgentinaFil: Lanusse, Carlos Edmundo. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaElsevier Science2010-09info: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/11336/112499Lifschitz, Adrian Luis; Entrocasso, Carlos M.; Alvarez, Luis Ignacio; Lloberas, Maria Mercedes; Ballent, Mariana; et al.; Interference with P-glycoprotein improves ivermectin activity against adult resistant nematodes in sheep; Elsevier Science; Veterinary Parasitology; 172; 3-4; 9-2010; 291-2980304-40171873-2550CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/http://linkinghub.elsevier.com/retrieve/pii/S030440171000275Xinfo:eu-repo/semantics/altIdentifier/doi/10.1016/j.vetpar.2010.04.039info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:53:59Zoai:ri.conicet.gov.ar:11336/112499instacron: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 09:54:00.343CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Interference with P-glycoprotein improves ivermectin activity against adult resistant nematodes in sheep
title Interference with P-glycoprotein improves ivermectin activity against adult resistant nematodes in sheep
spellingShingle Interference with P-glycoprotein improves ivermectin activity against adult resistant nematodes in sheep
Lifschitz, Adrian Luis
IVERMECTIN
SHEEP
RESISTANCE NEMATODES
PHARMACOKINETICS
title_short Interference with P-glycoprotein improves ivermectin activity against adult resistant nematodes in sheep
title_full Interference with P-glycoprotein improves ivermectin activity against adult resistant nematodes in sheep
title_fullStr Interference with P-glycoprotein improves ivermectin activity against adult resistant nematodes in sheep
title_full_unstemmed Interference with P-glycoprotein improves ivermectin activity against adult resistant nematodes in sheep
title_sort Interference with P-glycoprotein improves ivermectin activity against adult resistant nematodes in sheep
dc.creator.none.fl_str_mv Lifschitz, Adrian Luis
Entrocasso, Carlos M.
Alvarez, Luis Ignacio
Lloberas, Maria Mercedes
Ballent, Mariana
Manazza, Gustavo Oscar
Virkel, Guillermo Leon
Borda, Bernardino
Lanusse, Carlos Edmundo
author Lifschitz, Adrian Luis
author_facet Lifschitz, Adrian Luis
Entrocasso, Carlos M.
Alvarez, Luis Ignacio
Lloberas, Maria Mercedes
Ballent, Mariana
Manazza, Gustavo Oscar
Virkel, Guillermo Leon
Borda, Bernardino
Lanusse, Carlos Edmundo
author_role author
author2 Entrocasso, Carlos M.
Alvarez, Luis Ignacio
Lloberas, Maria Mercedes
Ballent, Mariana
Manazza, Gustavo Oscar
Virkel, Guillermo Leon
Borda, Bernardino
Lanusse, Carlos Edmundo
author2_role author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv IVERMECTIN
SHEEP
RESISTANCE NEMATODES
PHARMACOKINETICS
topic IVERMECTIN
SHEEP
RESISTANCE NEMATODES
PHARMACOKINETICS
purl_subject.fl_str_mv https://purl.org/becyt/ford/4.3
https://purl.org/becyt/ford/4
dc.description.none.fl_txt_mv The in vivo co-administration of ivermectin (IVM) with P-glycoprotein (P-gp) modulator agents has been shown to enhance its systemic availability. However, there is no sufficient evidence on the impact that this type of drug?drug interaction may have on the in vivo efficacy against resistant nematodes in ruminant species. The current work reports on the effects of loperamide (LPM), a P-gp modulating agent, on both IVM kinetic behaviour and anthelmintic activity in infected lambs. Eighteen (18) lambs naturally infected with IVM-resistant gastrointestinal nematodes were allocated into three (3) experimental groups. Group A remained as untreated control. Animals in Groups B and C received IVM (200 μg/kg, subcutaneously) either alone or co-administered with LPM (0.2 mg/kg, twice every 12 h), respectively. Individual faecal samples were collected from experimental animals at days −1 and 14 post-treatment to perform the faecal eggs count reduction test (FECRT). Blood samples were collected between 0 and 14 days post-treatment and IVM plasma concentrations were determined by HPLC. Additionally, at day 14 post-treatment, lambs from all experimental groups were sacrificed and adult gastrointestinal nematode counts were performed. FECRT values increased from 78.6 (IVM alone) to 96% (IVM + LPM). Haemonchus contortus was highly resistant to IVM. The IVM alone treatment was completely ineffective (0% efficacy) against adult H. contortus. This efficacy value increased up to 72.5% in the presence of LPM. The efficacy against Trichostrongylus colubriformis increased from 77.9% (IVM alone) to 96.3% (IVM + LPM). The described favorable tendency towards improved anthelmintic efficacy was in agreement with the enhanced IVM plasma availability (P < 0.05) and prolonged elimination half-life (P < 0.05) induced by LPM in infected lambs. A LPM-induced P-gp modulation increases IVM systemic exposure in the host but also it may reduce P-gp efflux transport over-expressed in target resistant nematodes
Fil: Lifschitz, Adrian Luis. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Entrocasso, Carlos M.. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Agencia de Extensión Rural Balcarce; Argentina
Fil: Alvarez, Luis Ignacio. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Lloberas, Maria Mercedes. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Agencia de Extensión Rural Balcarce; Argentina
Fil: Ballent, Mariana. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Manazza, Gustavo Oscar. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Agencia de Extensión Rural Balcarce; Argentina
Fil: Virkel, Guillermo Leon. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Borda, Bernardino. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Buenos Aires Sur. Estación Experimental Agropecuaria Balcarce. Agencia de Extensión Rural Balcarce; Argentina
Fil: Lanusse, Carlos Edmundo. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
description The in vivo co-administration of ivermectin (IVM) with P-glycoprotein (P-gp) modulator agents has been shown to enhance its systemic availability. However, there is no sufficient evidence on the impact that this type of drug?drug interaction may have on the in vivo efficacy against resistant nematodes in ruminant species. The current work reports on the effects of loperamide (LPM), a P-gp modulating agent, on both IVM kinetic behaviour and anthelmintic activity in infected lambs. Eighteen (18) lambs naturally infected with IVM-resistant gastrointestinal nematodes were allocated into three (3) experimental groups. Group A remained as untreated control. Animals in Groups B and C received IVM (200 μg/kg, subcutaneously) either alone or co-administered with LPM (0.2 mg/kg, twice every 12 h), respectively. Individual faecal samples were collected from experimental animals at days −1 and 14 post-treatment to perform the faecal eggs count reduction test (FECRT). Blood samples were collected between 0 and 14 days post-treatment and IVM plasma concentrations were determined by HPLC. Additionally, at day 14 post-treatment, lambs from all experimental groups were sacrificed and adult gastrointestinal nematode counts were performed. FECRT values increased from 78.6 (IVM alone) to 96% (IVM + LPM). Haemonchus contortus was highly resistant to IVM. The IVM alone treatment was completely ineffective (0% efficacy) against adult H. contortus. This efficacy value increased up to 72.5% in the presence of LPM. The efficacy against Trichostrongylus colubriformis increased from 77.9% (IVM alone) to 96.3% (IVM + LPM). The described favorable tendency towards improved anthelmintic efficacy was in agreement with the enhanced IVM plasma availability (P < 0.05) and prolonged elimination half-life (P < 0.05) induced by LPM in infected lambs. A LPM-induced P-gp modulation increases IVM systemic exposure in the host but also it may reduce P-gp efflux transport over-expressed in target resistant nematodes
publishDate 2010
dc.date.none.fl_str_mv 2010-09
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/11336/112499
Lifschitz, Adrian Luis; Entrocasso, Carlos M.; Alvarez, Luis Ignacio; Lloberas, Maria Mercedes; Ballent, Mariana; et al.; Interference with P-glycoprotein improves ivermectin activity against adult resistant nematodes in sheep; Elsevier Science; Veterinary Parasitology; 172; 3-4; 9-2010; 291-298
0304-4017
1873-2550
CONICET Digital
CONICET
url http://hdl.handle.net/11336/112499
identifier_str_mv Lifschitz, Adrian Luis; Entrocasso, Carlos M.; Alvarez, Luis Ignacio; Lloberas, Maria Mercedes; Ballent, Mariana; et al.; Interference with P-glycoprotein improves ivermectin activity against adult resistant nematodes in sheep; Elsevier Science; Veterinary Parasitology; 172; 3-4; 9-2010; 291-298
0304-4017
1873-2550
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/http://linkinghub.elsevier.com/retrieve/pii/S030440171000275X
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.vetpar.2010.04.039
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
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science
publisher.none.fl_str_mv Elsevier Science
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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score 13.13397

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