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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/106015
Ver los metadatos del registro completo
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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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1846083199130664960 |
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13.22299 |