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dc.contributor.author
Virkel, Guillermo Leon  
dc.contributor.author
Lifschitz, Adrian Luis  
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Sallovitz, Juan Manuel  
dc.contributor.author
Ballent, Mariana  
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Scarcella, Silvana Andrea  
dc.contributor.author
Lanusse, Carlos Edmundo  
dc.date.available
2019-09-18T19:20:47Z  
dc.date.issued
2009-08  
dc.identifier.citation
Virkel, Guillermo Leon; Lifschitz, Adrian Luis; Sallovitz, Juan Manuel; Ballent, Mariana; Scarcella, Silvana Andrea; et al.; Inhibition of cytochrome P450 activity enhances the systemic availability of triclabendazole metabolites in sheep; Wiley Blackwell Publishing, Inc; Journal of Veterinary Pharmacology and Therapeutics; 32; SUPPL. 1; 8-2009; 79-86  
dc.identifier.issn
0140-7783  
dc.identifier.uri
http://hdl.handle.net/11336/83859  
dc.description.abstract
Understanding the disposition kinetics and the pattern of metabolism is critical to optimise the flukicidal activity of triclabendazole (TCBZ) in ruminants. TCBZ is metabolised by both flavin-monooxygenase (FMO) and cytochrome P450 (P450) in the liver. Interference with these metabolic pathways may be useful to increase the systemic availabilities of TCBZ metabolites, which may improve the efficacy against Fasciola hepatica. The plasma disposition of TCBZ metabolites was evaluated following TCBZ co-administration with FMO [methimazole (MTZ)] and P450 [piperonyl butoxyde (PB) and ketoconazole (KTZ)] inhibitors in sheep. Twenty (20) healthy Corriedale x Merino weaned female lambs were randomly allocated into four experimental groups. Animals of each group were treated as follow: Group A, TCBZ alone (5 mg ⁄ kg, IV route); Group B, TCBZ (5 mg⁄ kg, IV) + MTZ (3 mg⁄ kg, IV); Group C, TCBZ (5 mg⁄ kg, IV) + PB (30 mg⁄ kg, IV) and Group D, TCBZ (5 mg⁄ kg, IV) + KTZ (10 mg⁄ kg, orally). Blood samples were taken over 240 h post-treatment and analysed by HPLC. TCBZ sulphoxide and sulphone were the main metabolites recovered in plasma. MTZ did not affect TCBZ disposition kinetics. TCBZ sulphoxide Cmax values were significantly increased (P < 0.05) after the TCBZ + PB (62%) and TCBZ + KTZ (37%) treatments compared to those measured in the TCBZ alone treatment. TCBZ sulphoxide plasma AUCs were higher (P < 0.05) in the presence of both PB (99%) and KTZ (41%). Inhibition of TCBZ P450-mediated oxidation in the liver accounted for the increased systemic availability of its active metabolite TCBZ sulphoxide. This work contributes to the search of different strategies to improve the use of this flukicidal drug in ruminants.  
dc.format
application/pdf  
dc.language.iso
eng  
dc.publisher
Wiley Blackwell Publishing, Inc  
dc.rights
info:eu-repo/semantics/openAccess  
dc.rights.uri
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/  
dc.subject
P450 Inhibition  
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Pharmacokinetics  
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Triclabendazole  
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Sheep  
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Ciencias Veterinarias  
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Ciencias Veterinarias  
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CIENCIAS AGRÍCOLAS  
dc.title
Inhibition of cytochrome P450 activity enhances the systemic availability of triclabendazole metabolites in sheep  
dc.type
info:eu-repo/semantics/article  
dc.type
info:ar-repo/semantics/artículo  
dc.type
info:eu-repo/semantics/publishedVersion  
dc.date.updated
2019-07-24T17:39:44Z  
dc.journal.volume
32  
dc.journal.number
SUPPL. 1  
dc.journal.pagination
79-86  
dc.journal.pais
Reino Unido  
dc.journal.ciudad
Londres  
dc.description.fil
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  
dc.description.fil
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  
dc.description.fil
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. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina  
dc.description.fil
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  
dc.description.fil
Fil: Scarcella, Silvana Andrea. 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  
dc.description.fil
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  
dc.journal.title
Journal of Veterinary Pharmacology and Therapeutics  
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2885.2008.01006.x