Pretreatment with the inducers rifampicin and phenobarbital alters ivermectin gastrointestinal disposition
- Autores
- Ballent, Mariana; Lifschitz, Adrian Luis; Virkel, Guillermo Leon; Maté, María Laura; Lanusse, Carlos Edmundo
- Año de publicación
- 2010
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- The goal of the study was to evaluate the effects of rifampicin (RFP) and phenobarbital (PBT) on the plasma and gastrointestinal disposition kinetics of ivermectin (IVM) subcutaneously administered to Wistar rats. Fifty seven rats were used. Animals in Group I were the noninduced (control) group. Those in Groups II and III received a treatment with RFP (160 mg/day) and PBT (35 mg/day), respectively, both given orally during eight consecutive days as induction regimen. The IVM pharmacokinetic study was started 24 h after the RFP and PBT last administration. Animals received IVM (200 μg/kg) by subcutaneous injection. Rats were sacrificed between 6 h and 3 days after IVM administration. Blood and samples of liver tissue, intestinal wall and luminal content of jejunum were collected from each animal. IVM concentrations were measured by high performance liquid chromatography. IVM disposition kinetics in plasma and tissues was significantly modified by the PBT treatment, but not by RFP. Despite the enhanced CYP3A activity observed after the pretreatment with RPF and PBT, there were no marked changes on the percentages of IVM metabolites recovered from the bloodstream in induced and noninduced animals. An enhanced P-glycoprotein-mediated intestinal transport activity in pretreated animals (particularly in PBT pretreated rats) may explain the drastic changes observed on IVM disposition.
Fil: Ballent, Mariana. 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: 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: Virkel, Guillermo Leon. 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: Maté, María Laura. 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: Lanusse, Carlos Edmundo. 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 - Materia
-
Ivermectin
Disposition
P-Glycoprotein
Inducers - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/83890
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Pretreatment with the inducers rifampicin and phenobarbital alters ivermectin gastrointestinal dispositionBallent, MarianaLifschitz, Adrian LuisVirkel, Guillermo LeonMaté, María LauraLanusse, Carlos EdmundoIvermectinDispositionP-GlycoproteinInducershttps://purl.org/becyt/ford/4.3https://purl.org/becyt/ford/4The goal of the study was to evaluate the effects of rifampicin (RFP) and phenobarbital (PBT) on the plasma and gastrointestinal disposition kinetics of ivermectin (IVM) subcutaneously administered to Wistar rats. Fifty seven rats were used. Animals in Group I were the noninduced (control) group. Those in Groups II and III received a treatment with RFP (160 mg/day) and PBT (35 mg/day), respectively, both given orally during eight consecutive days as induction regimen. The IVM pharmacokinetic study was started 24 h after the RFP and PBT last administration. Animals received IVM (200 μg/kg) by subcutaneous injection. Rats were sacrificed between 6 h and 3 days after IVM administration. Blood and samples of liver tissue, intestinal wall and luminal content of jejunum were collected from each animal. IVM concentrations were measured by high performance liquid chromatography. IVM disposition kinetics in plasma and tissues was significantly modified by the PBT treatment, but not by RFP. Despite the enhanced CYP3A activity observed after the pretreatment with RPF and PBT, there were no marked changes on the percentages of IVM metabolites recovered from the bloodstream in induced and noninduced animals. An enhanced P-glycoprotein-mediated intestinal transport activity in pretreated animals (particularly in PBT pretreated rats) may explain the drastic changes observed on IVM disposition.Fil: Ballent, Mariana. 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: 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: Virkel, Guillermo Leon. 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: Maté, María Laura. 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: Lanusse, Carlos Edmundo. 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; ArgentinaWiley Blackwell Publishing, Inc2010-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/83890Ballent, Mariana; Lifschitz, Adrian Luis; Virkel, Guillermo Leon; Maté, María Laura; Lanusse, Carlos Edmundo; Pretreatment with the inducers rifampicin and phenobarbital alters ivermectin gastrointestinal disposition; Wiley Blackwell Publishing, Inc; Journal of Veterinary Pharmacology and Therapeutics; 33; 3; 7-2010; 252-2590140-7783CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2885.2009.01129.xinfo:eu-repo/semantics/altIdentifier/doi/10.1111/j.1365-2885.2009.01129.xinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:42:47Zoai:ri.conicet.gov.ar:11336/83890instacron: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:34982025-09-29 10:42:47.789CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Pretreatment with the inducers rifampicin and phenobarbital alters ivermectin gastrointestinal disposition |
title |
Pretreatment with the inducers rifampicin and phenobarbital alters ivermectin gastrointestinal disposition |
spellingShingle |
Pretreatment with the inducers rifampicin and phenobarbital alters ivermectin gastrointestinal disposition Ballent, Mariana Ivermectin Disposition P-Glycoprotein Inducers |
title_short |
Pretreatment with the inducers rifampicin and phenobarbital alters ivermectin gastrointestinal disposition |
title_full |
Pretreatment with the inducers rifampicin and phenobarbital alters ivermectin gastrointestinal disposition |
title_fullStr |
Pretreatment with the inducers rifampicin and phenobarbital alters ivermectin gastrointestinal disposition |
title_full_unstemmed |
Pretreatment with the inducers rifampicin and phenobarbital alters ivermectin gastrointestinal disposition |
title_sort |
Pretreatment with the inducers rifampicin and phenobarbital alters ivermectin gastrointestinal disposition |
dc.creator.none.fl_str_mv |
Ballent, Mariana Lifschitz, Adrian Luis Virkel, Guillermo Leon Maté, María Laura Lanusse, Carlos Edmundo |
author |
Ballent, Mariana |
author_facet |
Ballent, Mariana Lifschitz, Adrian Luis Virkel, Guillermo Leon Maté, María Laura Lanusse, Carlos Edmundo |
author_role |
author |
author2 |
Lifschitz, Adrian Luis Virkel, Guillermo Leon Maté, María Laura Lanusse, Carlos Edmundo |
author2_role |
author author author author |
dc.subject.none.fl_str_mv |
Ivermectin Disposition P-Glycoprotein Inducers |
topic |
Ivermectin Disposition P-Glycoprotein Inducers |
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 goal of the study was to evaluate the effects of rifampicin (RFP) and phenobarbital (PBT) on the plasma and gastrointestinal disposition kinetics of ivermectin (IVM) subcutaneously administered to Wistar rats. Fifty seven rats were used. Animals in Group I were the noninduced (control) group. Those in Groups II and III received a treatment with RFP (160 mg/day) and PBT (35 mg/day), respectively, both given orally during eight consecutive days as induction regimen. The IVM pharmacokinetic study was started 24 h after the RFP and PBT last administration. Animals received IVM (200 μg/kg) by subcutaneous injection. Rats were sacrificed between 6 h and 3 days after IVM administration. Blood and samples of liver tissue, intestinal wall and luminal content of jejunum were collected from each animal. IVM concentrations were measured by high performance liquid chromatography. IVM disposition kinetics in plasma and tissues was significantly modified by the PBT treatment, but not by RFP. Despite the enhanced CYP3A activity observed after the pretreatment with RPF and PBT, there were no marked changes on the percentages of IVM metabolites recovered from the bloodstream in induced and noninduced animals. An enhanced P-glycoprotein-mediated intestinal transport activity in pretreated animals (particularly in PBT pretreated rats) may explain the drastic changes observed on IVM disposition. Fil: Ballent, Mariana. 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: 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: Virkel, Guillermo Leon. 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: Maté, María Laura. 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: Lanusse, Carlos Edmundo. 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 |
description |
The goal of the study was to evaluate the effects of rifampicin (RFP) and phenobarbital (PBT) on the plasma and gastrointestinal disposition kinetics of ivermectin (IVM) subcutaneously administered to Wistar rats. Fifty seven rats were used. Animals in Group I were the noninduced (control) group. Those in Groups II and III received a treatment with RFP (160 mg/day) and PBT (35 mg/day), respectively, both given orally during eight consecutive days as induction regimen. The IVM pharmacokinetic study was started 24 h after the RFP and PBT last administration. Animals received IVM (200 μg/kg) by subcutaneous injection. Rats were sacrificed between 6 h and 3 days after IVM administration. Blood and samples of liver tissue, intestinal wall and luminal content of jejunum were collected from each animal. IVM concentrations were measured by high performance liquid chromatography. IVM disposition kinetics in plasma and tissues was significantly modified by the PBT treatment, but not by RFP. Despite the enhanced CYP3A activity observed after the pretreatment with RPF and PBT, there were no marked changes on the percentages of IVM metabolites recovered from the bloodstream in induced and noninduced animals. An enhanced P-glycoprotein-mediated intestinal transport activity in pretreated animals (particularly in PBT pretreated rats) may explain the drastic changes observed on IVM disposition. |
publishDate |
2010 |
dc.date.none.fl_str_mv |
2010-07 |
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/11336/83890 Ballent, Mariana; Lifschitz, Adrian Luis; Virkel, Guillermo Leon; Maté, María Laura; Lanusse, Carlos Edmundo; Pretreatment with the inducers rifampicin and phenobarbital alters ivermectin gastrointestinal disposition; Wiley Blackwell Publishing, Inc; Journal of Veterinary Pharmacology and Therapeutics; 33; 3; 7-2010; 252-259 0140-7783 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/83890 |
identifier_str_mv |
Ballent, Mariana; Lifschitz, Adrian Luis; Virkel, Guillermo Leon; Maté, María Laura; Lanusse, Carlos Edmundo; Pretreatment with the inducers rifampicin and phenobarbital alters ivermectin gastrointestinal disposition; Wiley Blackwell Publishing, Inc; Journal of Veterinary Pharmacology and Therapeutics; 33; 3; 7-2010; 252-259 0140-7783 CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2885.2009.01129.x info:eu-repo/semantics/altIdentifier/doi/10.1111/j.1365-2885.2009.01129.x |
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 application/pdf |
dc.publisher.none.fl_str_mv |
Wiley Blackwell Publishing, Inc |
publisher.none.fl_str_mv |
Wiley Blackwell Publishing, Inc |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) |
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CONICET Digital (CONICET) |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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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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1844614461260824576 |
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13.070432 |