Sex-related differences in the gastrointestinal disposition of ivermectin in the rat: P-glycoprotein involvement and itraconazole modulation

Autores
Lifschitz, Adrian Luis; Ballent, Mariana; Virkel, Guillermo Leon; Sallovitz, Juan Manuel; Lanusse, Carlos Edmundo
Año de publicación
2006
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Ivermectin (IVM), a macrocyclic lactone used as antiparasite agent, has been reported as a P‐glycoprotein (P‐gp) substrate. The participation of P‐gp in the IVM excretion process has been previously demonstrated. Sex‐related differences in the kinetic behaviour of some macrocyclic lactone compounds have been observed. The aim of this work was to characterize in‐vivo the comparative gastrointestinal disposition of IVM in male and female rats. The sex‐related influence on the itraconazole (ITZ) modulation of P‐gp‐mediated IVM intestinal transport was also assessed. Sixty Wistar rats (30 male, 30 female) received IVM alone or co‐administered with ITZ. Rats were killed between 6 and 72h after treatment and blood, gastrointestinal tissues and lumen contents were collected. IVM concentrations were determined by high performance liquid chromatography. Substantial sex‐related differences in the IVM disposition kinetics were observed. Higher IVM systemic availability was observed in female rats. The ITZ‐mediated modulation of the IVM disposition kinetics had a differential impact between male and female rats. Co‐administration with ITZ resulted in a marked increase in the IVM concentrations in the wall tissue from different portions of the gastrointestinal tract of male rats. The presence of ITZ induced drastic sex‐related changes on the P‐gp‐mediated IVM gastrointestinal disposition.
Fil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; 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: 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: Sallovitz, Juan Manuel. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; 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 GASTROINTESTINAL DISPOSITION
IVERMECTIN
ITRACONAZOLE MODULATION
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:11336/104976
Acceder
id CONICETDig_19d7e96b62ca93703b3c48416fd0196b
oai_identifier_str oai:ri.conicet.gov.ar:11336/104976
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Sex-related differences in the gastrointestinal disposition of ivermectin in the rat: P-glycoprotein involvement and itraconazole modulationLifschitz, Adrian LuisBallent, MarianaVirkel, Guillermo LeonSallovitz, Juan ManuelLanusse, Carlos EdmundoIVERMECTIN GASTROINTESTINAL DISPOSITIONIVERMECTINITRACONAZOLE MODULATIONhttps://purl.org/becyt/ford/4.3https://purl.org/becyt/ford/4Ivermectin (IVM), a macrocyclic lactone used as antiparasite agent, has been reported as a P‐glycoprotein (P‐gp) substrate. The participation of P‐gp in the IVM excretion process has been previously demonstrated. Sex‐related differences in the kinetic behaviour of some macrocyclic lactone compounds have been observed. The aim of this work was to characterize in‐vivo the comparative gastrointestinal disposition of IVM in male and female rats. The sex‐related influence on the itraconazole (ITZ) modulation of P‐gp‐mediated IVM intestinal transport was also assessed. Sixty Wistar rats (30 male, 30 female) received IVM alone or co‐administered with ITZ. Rats were killed between 6 and 72h after treatment and blood, gastrointestinal tissues and lumen contents were collected. IVM concentrations were determined by high performance liquid chromatography. Substantial sex‐related differences in the IVM disposition kinetics were observed. Higher IVM systemic availability was observed in female rats. The ITZ‐mediated modulation of the IVM disposition kinetics had a differential impact between male and female rats. Co‐administration with ITZ resulted in a marked increase in the IVM concentrations in the wall tissue from different portions of the gastrointestinal tract of male rats. The presence of ITZ induced drastic sex‐related changes on the P‐gp‐mediated IVM gastrointestinal disposition.Fil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; 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: 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: Sallovitz, Juan Manuel. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; 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; ArgentinaPharmaceutical Press-Royal Pharmaceutical Society Great Britian2006-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/104976Lifschitz, Adrian Luis; Ballent, Mariana; Virkel, Guillermo Leon; Sallovitz, Juan Manuel; Lanusse, Carlos Edmundo; Sex-related differences in the gastrointestinal disposition of ivermectin in the rat: P-glycoprotein involvement and itraconazole modulation; Pharmaceutical Press-Royal Pharmaceutical Society Great Britian; Journal of Pharmacy and Pharmacology; 58; 8; 8-2006; 1055-10620022-35732042-7158CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1211/jpp.58.8.0005info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1211/jpp.58.8.0005info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:06:39Zoai:ri.conicet.gov.ar:11336/104976instacron: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 13:06:39.657CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Sex-related differences in the gastrointestinal disposition of ivermectin in the rat: P-glycoprotein involvement and itraconazole modulation
title Sex-related differences in the gastrointestinal disposition of ivermectin in the rat: P-glycoprotein involvement and itraconazole modulation
spellingShingle Sex-related differences in the gastrointestinal disposition of ivermectin in the rat: P-glycoprotein involvement and itraconazole modulation
Lifschitz, Adrian Luis
IVERMECTIN GASTROINTESTINAL DISPOSITION
IVERMECTIN
ITRACONAZOLE MODULATION
title_short Sex-related differences in the gastrointestinal disposition of ivermectin in the rat: P-glycoprotein involvement and itraconazole modulation
title_full Sex-related differences in the gastrointestinal disposition of ivermectin in the rat: P-glycoprotein involvement and itraconazole modulation
title_fullStr Sex-related differences in the gastrointestinal disposition of ivermectin in the rat: P-glycoprotein involvement and itraconazole modulation
title_full_unstemmed Sex-related differences in the gastrointestinal disposition of ivermectin in the rat: P-glycoprotein involvement and itraconazole modulation
title_sort Sex-related differences in the gastrointestinal disposition of ivermectin in the rat: P-glycoprotein involvement and itraconazole modulation
dc.creator.none.fl_str_mv Lifschitz, Adrian Luis
Ballent, Mariana
Virkel, Guillermo Leon
Sallovitz, Juan Manuel
Lanusse, Carlos Edmundo
author Lifschitz, Adrian Luis
author_facet Lifschitz, Adrian Luis
Ballent, Mariana
Virkel, Guillermo Leon
Sallovitz, Juan Manuel
Lanusse, Carlos Edmundo
author_role author
author2 Ballent, Mariana
Virkel, Guillermo Leon
Sallovitz, Juan Manuel
Lanusse, Carlos Edmundo
author2_role author
author
author
author
dc.subject.none.fl_str_mv IVERMECTIN GASTROINTESTINAL DISPOSITION
IVERMECTIN
ITRACONAZOLE MODULATION
topic IVERMECTIN GASTROINTESTINAL DISPOSITION
IVERMECTIN
ITRACONAZOLE MODULATION
purl_subject.fl_str_mv https://purl.org/becyt/ford/4.3
https://purl.org/becyt/ford/4
dc.description.none.fl_txt_mv Ivermectin (IVM), a macrocyclic lactone used as antiparasite agent, has been reported as a P‐glycoprotein (P‐gp) substrate. The participation of P‐gp in the IVM excretion process has been previously demonstrated. Sex‐related differences in the kinetic behaviour of some macrocyclic lactone compounds have been observed. The aim of this work was to characterize in‐vivo the comparative gastrointestinal disposition of IVM in male and female rats. The sex‐related influence on the itraconazole (ITZ) modulation of P‐gp‐mediated IVM intestinal transport was also assessed. Sixty Wistar rats (30 male, 30 female) received IVM alone or co‐administered with ITZ. Rats were killed between 6 and 72h after treatment and blood, gastrointestinal tissues and lumen contents were collected. IVM concentrations were determined by high performance liquid chromatography. Substantial sex‐related differences in the IVM disposition kinetics were observed. Higher IVM systemic availability was observed in female rats. The ITZ‐mediated modulation of the IVM disposition kinetics had a differential impact between male and female rats. Co‐administration with ITZ resulted in a marked increase in the IVM concentrations in the wall tissue from different portions of the gastrointestinal tract of male rats. The presence of ITZ induced drastic sex‐related changes on the P‐gp‐mediated IVM gastrointestinal disposition.
Fil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; 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: 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: Sallovitz, Juan Manuel. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; 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 Ivermectin (IVM), a macrocyclic lactone used as antiparasite agent, has been reported as a P‐glycoprotein (P‐gp) substrate. The participation of P‐gp in the IVM excretion process has been previously demonstrated. Sex‐related differences in the kinetic behaviour of some macrocyclic lactone compounds have been observed. The aim of this work was to characterize in‐vivo the comparative gastrointestinal disposition of IVM in male and female rats. The sex‐related influence on the itraconazole (ITZ) modulation of P‐gp‐mediated IVM intestinal transport was also assessed. Sixty Wistar rats (30 male, 30 female) received IVM alone or co‐administered with ITZ. Rats were killed between 6 and 72h after treatment and blood, gastrointestinal tissues and lumen contents were collected. IVM concentrations were determined by high performance liquid chromatography. Substantial sex‐related differences in the IVM disposition kinetics were observed. Higher IVM systemic availability was observed in female rats. The ITZ‐mediated modulation of the IVM disposition kinetics had a differential impact between male and female rats. Co‐administration with ITZ resulted in a marked increase in the IVM concentrations in the wall tissue from different portions of the gastrointestinal tract of male rats. The presence of ITZ induced drastic sex‐related changes on the P‐gp‐mediated IVM gastrointestinal disposition.
publishDate 2006
dc.date.none.fl_str_mv 2006-08
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/11336/104976
Lifschitz, Adrian Luis; Ballent, Mariana; Virkel, Guillermo Leon; Sallovitz, Juan Manuel; Lanusse, Carlos Edmundo; Sex-related differences in the gastrointestinal disposition of ivermectin in the rat: P-glycoprotein involvement and itraconazole modulation; Pharmaceutical Press-Royal Pharmaceutical Society Great Britian; Journal of Pharmacy and Pharmacology; 58; 8; 8-2006; 1055-1062
0022-3573
2042-7158
CONICET Digital
CONICET
url http://hdl.handle.net/11336/104976
identifier_str_mv Lifschitz, Adrian Luis; Ballent, Mariana; Virkel, Guillermo Leon; Sallovitz, Juan Manuel; Lanusse, Carlos Edmundo; Sex-related differences in the gastrointestinal disposition of ivermectin in the rat: P-glycoprotein involvement and itraconazole modulation; Pharmaceutical Press-Royal Pharmaceutical Society Great Britian; Journal of Pharmacy and Pharmacology; 58; 8; 8-2006; 1055-1062
0022-3573
2042-7158
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1211/jpp.58.8.0005
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1211/jpp.58.8.0005
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
dc.publisher.none.fl_str_mv Pharmaceutical Press-Royal Pharmaceutical Society Great Britian
publisher.none.fl_str_mv Pharmaceutical Press-Royal Pharmaceutical Society Great Britian
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_ 1842980281032638464
score 13.004268

Publicaciones similares