Effects of formulation concentration on intravenous pharmacokinetics, chirality and in vitro solubility of oxfendazole and its metabolites in sheep

Autores
Sanchez Bruni, Sergio Fabian; Jones, Douglas G.; Small, John; McKellar, Quintin A.
Año de publicación
2005
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
This study compared pharmacokinetic (PK) profiles in sheep dosed intravenously with three different concentrations of oxfendazole (OFZ).  An in vitro plasma OFZ dissolution study provided additional information on plasma saturation.  For the PK study, 18 adult, parasite-free, female Suffolk cross sheep, allocated into three groups (n=6), were treated intravenously, at a dose rate of 5mg/kg bodyweight, with aqueous solutions containing at 4, 8 or 16% OFZ.  Plasma drug concentrations were measured, for up to 72 hours post-treatment, by a validated high performance liquid chromatography (HPLC) method with UV detection.  OFZ and fenbendazole sulphone (FBZSO2) were the main metabolites detected in all three experimental groups. In animals given the 4% solution, OFZ depleted according to a biexponential concentration vs. time curve.  In contrast, those given 8 or 16% preparations produced atypical curves fitted by monoexponential equations. No statistically significant differences in area under concentration-time curves (AUC) were observed, but concentration-dependent differences in distribution and mean residence time (MRT) were evident.  Compared with 4% OFZ, animals treated with 8 and 16% formulations had slower half-lives of metabolite formation,and lower AUC’s, suggesting that OFZ sulphonation may have been modified.  In vitro there was evidence of plasma saturation and precipitation associated with 8 and 16% OFZ preparations.  It is concluded that differences in PK profiles, in vivo, may have been related to inadequate dissolution and/or tissue drug precipitation.
Fil: Sanchez Bruni, Sergio Fabian. 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: Jones, Douglas G.. Moredun Research Institute. Pentlands Science Park; Reino Unido
Fil: Small, John. Moredun Research Institute. Pentlands Science Park; Reino Unido
Fil: McKellar, Quintin A.. Moredun Research Institute. Pentlands Science Park; Reino Unido
Materia
PHARMACOKINETICS
BENZIMIDAZOLES
CHILARITY
SHEEP
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:11336/106015

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network_name_str CONICET Digital (CONICET)
spelling Effects of formulation concentration on intravenous pharmacokinetics, chirality and in vitro solubility of oxfendazole and its metabolites in sheepSanchez Bruni, Sergio FabianJones, Douglas G.Small, JohnMcKellar, Quintin A.PHARMACOKINETICSBENZIMIDAZOLESCHILARITYSHEEPhttps://purl.org/becyt/ford/4.3https://purl.org/becyt/ford/4This study compared pharmacokinetic (PK) profiles in sheep dosed intravenously with three different concentrations of oxfendazole (OFZ).  An in vitro plasma OFZ dissolution study provided additional information on plasma saturation.  For the PK study, 18 adult, parasite-free, female Suffolk cross sheep, allocated into three groups (n=6), were treated intravenously, at a dose rate of 5mg/kg bodyweight, with aqueous solutions containing at 4, 8 or 16% OFZ.  Plasma drug concentrations were measured, for up to 72 hours post-treatment, by a validated high performance liquid chromatography (HPLC) method with UV detection.  OFZ and fenbendazole sulphone (FBZSO2) were the main metabolites detected in all three experimental groups. In animals given the 4% solution, OFZ depleted according to a biexponential concentration vs. time curve.  In contrast, those given 8 or 16% preparations produced atypical curves fitted by monoexponential equations. No statistically significant differences in area under concentration-time curves (AUC) were observed, but concentration-dependent differences in distribution and mean residence time (MRT) were evident.  Compared with 4% OFZ, animals treated with 8 and 16% formulations had slower half-lives of metabolite formation,and lower AUC’s, suggesting that OFZ sulphonation may have been modified.  In vitro there was evidence of plasma saturation and precipitation associated with 8 and 16% OFZ preparations.  It is concluded that differences in PK profiles, in vivo, may have been related to inadequate dissolution and/or tissue drug precipitation.Fil: Sanchez Bruni, Sergio Fabian. 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: Jones, Douglas G.. Moredun Research Institute. Pentlands Science Park; Reino UnidoFil: Small, John. Moredun Research Institute. Pentlands Science Park; Reino UnidoFil: McKellar, Quintin A.. Moredun Research Institute. Pentlands Science Park; Reino UnidoWiley Blackwell Publishing, Inc2005-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/106015Sanchez Bruni, Sergio Fabian; Jones, Douglas G.; Small, John; McKellar, Quintin A.; Effects of formulation concentration on intravenous pharmacokinetics, chirality and in vitro solubility of oxfendazole and its metabolites in sheep; Wiley Blackwell Publishing, Inc; Journal of Veterinary Pharmacology and Therapeutics; 28; 5; 10-2005; 467-4730140-77831365-2885CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1111/j.1365-2885.2005.00678.xinfo:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2885.2005.00678.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 Técnicas2025-10-15T15:05:40Zoai:ri.conicet.gov.ar:11336/106015instacron: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:34982025-10-15 15:05:40.428CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Effects of formulation concentration on intravenous pharmacokinetics, chirality and in vitro solubility of oxfendazole and its metabolites in sheep
title Effects of formulation concentration on intravenous pharmacokinetics, chirality and in vitro solubility of oxfendazole and its metabolites in sheep
spellingShingle Effects of formulation concentration on intravenous pharmacokinetics, chirality and in vitro solubility of oxfendazole and its metabolites in sheep
Sanchez Bruni, Sergio Fabian
PHARMACOKINETICS
BENZIMIDAZOLES
CHILARITY
SHEEP
title_short Effects of formulation concentration on intravenous pharmacokinetics, chirality and in vitro solubility of oxfendazole and its metabolites in sheep
title_full Effects of formulation concentration on intravenous pharmacokinetics, chirality and in vitro solubility of oxfendazole and its metabolites in sheep
title_fullStr Effects of formulation concentration on intravenous pharmacokinetics, chirality and in vitro solubility of oxfendazole and its metabolites in sheep
title_full_unstemmed Effects of formulation concentration on intravenous pharmacokinetics, chirality and in vitro solubility of oxfendazole and its metabolites in sheep
title_sort Effects of formulation concentration on intravenous pharmacokinetics, chirality and in vitro solubility of oxfendazole and its metabolites in sheep
dc.creator.none.fl_str_mv Sanchez Bruni, Sergio Fabian
Jones, Douglas G.
Small, John
McKellar, Quintin A.
author Sanchez Bruni, Sergio Fabian
author_facet Sanchez Bruni, Sergio Fabian
Jones, Douglas G.
Small, John
McKellar, Quintin A.
author_role author
author2 Jones, Douglas G.
Small, John
McKellar, Quintin A.
author2_role author
author
author
dc.subject.none.fl_str_mv PHARMACOKINETICS
BENZIMIDAZOLES
CHILARITY
SHEEP
topic PHARMACOKINETICS
BENZIMIDAZOLES
CHILARITY
SHEEP
purl_subject.fl_str_mv https://purl.org/becyt/ford/4.3
https://purl.org/becyt/ford/4
dc.description.none.fl_txt_mv This study compared pharmacokinetic (PK) profiles in sheep dosed intravenously with three different concentrations of oxfendazole (OFZ).  An in vitro plasma OFZ dissolution study provided additional information on plasma saturation.  For the PK study, 18 adult, parasite-free, female Suffolk cross sheep, allocated into three groups (n=6), were treated intravenously, at a dose rate of 5mg/kg bodyweight, with aqueous solutions containing at 4, 8 or 16% OFZ.  Plasma drug concentrations were measured, for up to 72 hours post-treatment, by a validated high performance liquid chromatography (HPLC) method with UV detection.  OFZ and fenbendazole sulphone (FBZSO2) were the main metabolites detected in all three experimental groups. In animals given the 4% solution, OFZ depleted according to a biexponential concentration vs. time curve.  In contrast, those given 8 or 16% preparations produced atypical curves fitted by monoexponential equations. No statistically significant differences in area under concentration-time curves (AUC) were observed, but concentration-dependent differences in distribution and mean residence time (MRT) were evident.  Compared with 4% OFZ, animals treated with 8 and 16% formulations had slower half-lives of metabolite formation,and lower AUC’s, suggesting that OFZ sulphonation may have been modified.  In vitro there was evidence of plasma saturation and precipitation associated with 8 and 16% OFZ preparations.  It is concluded that differences in PK profiles, in vivo, may have been related to inadequate dissolution and/or tissue drug precipitation.
Fil: Sanchez Bruni, Sergio Fabian. 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: Jones, Douglas G.. Moredun Research Institute. Pentlands Science Park; Reino Unido
Fil: Small, John. Moredun Research Institute. Pentlands Science Park; Reino Unido
Fil: McKellar, Quintin A.. Moredun Research Institute. Pentlands Science Park; Reino Unido
description This study compared pharmacokinetic (PK) profiles in sheep dosed intravenously with three different concentrations of oxfendazole (OFZ).  An in vitro plasma OFZ dissolution study provided additional information on plasma saturation.  For the PK study, 18 adult, parasite-free, female Suffolk cross sheep, allocated into three groups (n=6), were treated intravenously, at a dose rate of 5mg/kg bodyweight, with aqueous solutions containing at 4, 8 or 16% OFZ.  Plasma drug concentrations were measured, for up to 72 hours post-treatment, by a validated high performance liquid chromatography (HPLC) method with UV detection.  OFZ and fenbendazole sulphone (FBZSO2) were the main metabolites detected in all three experimental groups. In animals given the 4% solution, OFZ depleted according to a biexponential concentration vs. time curve.  In contrast, those given 8 or 16% preparations produced atypical curves fitted by monoexponential equations. No statistically significant differences in area under concentration-time curves (AUC) were observed, but concentration-dependent differences in distribution and mean residence time (MRT) were evident.  Compared with 4% OFZ, animals treated with 8 and 16% formulations had slower half-lives of metabolite formation,and lower AUC’s, suggesting that OFZ sulphonation may have been modified.  In vitro there was evidence of plasma saturation and precipitation associated with 8 and 16% OFZ preparations.  It is concluded that differences in PK profiles, in vivo, may have been related to inadequate dissolution and/or tissue drug precipitation.
publishDate 2005
dc.date.none.fl_str_mv 2005-10
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/11336/106015
Sanchez Bruni, Sergio Fabian; Jones, Douglas G.; Small, John; McKellar, Quintin A.; Effects of formulation concentration on intravenous pharmacokinetics, chirality and in vitro solubility of oxfendazole and its metabolites in sheep; Wiley Blackwell Publishing, Inc; Journal of Veterinary Pharmacology and Therapeutics; 28; 5; 10-2005; 467-473
0140-7783
1365-2885
CONICET Digital
CONICET
url http://hdl.handle.net/11336/106015
identifier_str_mv Sanchez Bruni, Sergio Fabian; Jones, Douglas G.; Small, John; McKellar, Quintin A.; Effects of formulation concentration on intravenous pharmacokinetics, chirality and in vitro solubility of oxfendazole and its metabolites in sheep; Wiley Blackwell Publishing, Inc; Journal of Veterinary Pharmacology and Therapeutics; 28; 5; 10-2005; 467-473
0140-7783
1365-2885
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1111/j.1365-2885.2005.00678.x
info:eu-repo/semantics/altIdentifier/url/https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2885.2005.00678.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
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
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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