Artículo
Pretreatment with the inducers rifampicin and phenobarbital alters ivermectin gastrointestinal disposition
Ballent, Mariana
; Lifschitz, Adrian Luis
; Virkel, Guillermo Leon
; Maté, María Laura
; Lanusse, Carlos Edmundo
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Fecha de publicación:
07/2010
Editorial:
Wiley Blackwell Publishing, Inc
Revista:
Journal of Veterinary Pharmacology and Therapeutics
ISSN:
0140-7783
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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.
Palabras clave:
Ivermectin
,
Disposition
,
P-Glycoprotein
,
Inducers
Archivos asociados
Licencia
Identificadores
Colecciones
Articulos(CCT - TANDIL)
Articulos de CTRO CIENTIFICO TECNOLOGICO CONICET - TANDIL
Articulos de CTRO CIENTIFICO TECNOLOGICO CONICET - TANDIL
Articulos(CIVETAN)
Articulos de CENTRO DE INVESTIGACION VETERINARIA DE TANDIL
Articulos de CENTRO DE INVESTIGACION VETERINARIA DE TANDIL
Citación
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
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