Transtegumental diffusion of benzimidazole anthelmintics into Moniezia benedeni: correlation with their octanol–water partition coefficients

Autores
Mottier, Maria de Lourdes; Alvarez, Luis Ignacio; Pis, Ma. Alejandra; Lanusse, Carlos Edmundo
Año de publicación
2003
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The experiments described here report on the correlation between the ex vivo diffusion of different benzimidazole (BZD) anthelmintics into the cestode parasite Moniezia benedeni, and their octanol–water partition coefficients (P.C.). The characterisation of the drug diffusion process into target parasites is relevant to understand the mechanism of drug penetration and the pharmacological activity of anthelmintic drugs. Specimens of the tapeworm M. benedeni, used as a helminth parasite model, were obtained from untreated cattle killed at the local abattoir. The collected parasites were incubated (5–210 min) with either fenbendazole (FBZ),albendazole (ABZ), ricobendazole (RBZ), oxfendazole (OFZ), mebendazole (MBZ), oxibendazole (OBZ), or thiabendazole (TBZ), in a Kreb’s Ringer Tris buffer medium at a final concentration of 5 nmol/ml. After the incubation time elapsed, samples of parasite material were chemically extracted and prepared for high performance liquid chromatography (HPLC) analysis to measure drug/metabolite concentrations. Additionally, the octanol–water P.C. for each molecule was estimated as an indicator of drug lipophilicity,using reversed phase HPLC analysis. All the incubated drugs were recovered from the tapeworms as early as 5 min post incubation. There was a high correlation (r ¼ 0:87) between drug lipophilicity, expressed as octanol–water P.C. (Log P), and drug availability within the parasite. The most lipophilic BZD compounds (FBZ, ABZ, and MBZ), with P.C. values higher than 3.7, were measured at significative higher concentrations within the tapeworm compared to those drugs with the lowest P.C. values. Considering the results from the current and previous studies, it is clear that passive diffusion is a major mechanism of BZD penetration into cestode parasites, where lipid solubility is a determinant factor influencing the diffusion of these anthelmintic molecules through the parasite tegument.
Fil: Mottier, Maria de Lourdes. 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: Alvarez, Luis Ignacio. 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: Pis, Ma. Alejandra. 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. 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
Materia
BENZIMIDAZOLE
ANTHELMINTICS
MONIEZIA BENEDENI
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:11336/106799
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Transtegumental diffusion of benzimidazole anthelmintics into Moniezia benedeni: correlation with their octanol–water partition coefficientsMottier, Maria de LourdesAlvarez, Luis IgnacioPis, Ma. AlejandraLanusse, Carlos EdmundoBENZIMIDAZOLEANTHELMINTICSMONIEZIA BENEDENIhttps://purl.org/becyt/ford/4.3https://purl.org/becyt/ford/4The experiments described here report on the correlation between the ex vivo diffusion of different benzimidazole (BZD) anthelmintics into the cestode parasite Moniezia benedeni, and their octanol–water partition coefficients (P.C.). The characterisation of the drug diffusion process into target parasites is relevant to understand the mechanism of drug penetration and the pharmacological activity of anthelmintic drugs. Specimens of the tapeworm M. benedeni, used as a helminth parasite model, were obtained from untreated cattle killed at the local abattoir. The collected parasites were incubated (5–210 min) with either fenbendazole (FBZ),albendazole (ABZ), ricobendazole (RBZ), oxfendazole (OFZ), mebendazole (MBZ), oxibendazole (OBZ), or thiabendazole (TBZ), in a Kreb’s Ringer Tris buffer medium at a final concentration of 5 nmol/ml. After the incubation time elapsed, samples of parasite material were chemically extracted and prepared for high performance liquid chromatography (HPLC) analysis to measure drug/metabolite concentrations. Additionally, the octanol–water P.C. for each molecule was estimated as an indicator of drug lipophilicity,using reversed phase HPLC analysis. All the incubated drugs were recovered from the tapeworms as early as 5 min post incubation. There was a high correlation (r ¼ 0:87) between drug lipophilicity, expressed as octanol–water P.C. (Log P), and drug availability within the parasite. The most lipophilic BZD compounds (FBZ, ABZ, and MBZ), with P.C. values higher than 3.7, were measured at significative higher concentrations within the tapeworm compared to those drugs with the lowest P.C. values. Considering the results from the current and previous studies, it is clear that passive diffusion is a major mechanism of BZD penetration into cestode parasites, where lipid solubility is a determinant factor influencing the diffusion of these anthelmintic molecules through the parasite tegument.Fil: Mottier, Maria de Lourdes. 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: Alvarez, Luis Ignacio. 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: Pis, Ma. Alejandra. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias. Departamento de Fisiopatología. Laboratorio de Farmacología; ArgentinaFil: Lanusse, Carlos Edmundo. 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; ArgentinaAcademic Press Inc Elsevier Science2003-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/106799Mottier, Maria de Lourdes; Alvarez, Luis Ignacio; Pis, Ma. Alejandra; Lanusse, Carlos Edmundo; Transtegumental diffusion of benzimidazole anthelmintics into Moniezia benedeni: correlation with their octanol–water partition coefficients; Academic Press Inc Elsevier Science; Experimental Parasitology; 103; 1-2; 1-2003; 1-70014-48941090-2449CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1016/S0014-4894(03)00060-2info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0014489403000602info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:05:04Zoai:ri.conicet.gov.ar:11336/106799instacron: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 10:05:04.915CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Transtegumental diffusion of benzimidazole anthelmintics into Moniezia benedeni: correlation with their octanol–water partition coefficients
title Transtegumental diffusion of benzimidazole anthelmintics into Moniezia benedeni: correlation with their octanol–water partition coefficients
spellingShingle Transtegumental diffusion of benzimidazole anthelmintics into Moniezia benedeni: correlation with their octanol–water partition coefficients
Mottier, Maria de Lourdes
BENZIMIDAZOLE
ANTHELMINTICS
MONIEZIA BENEDENI
title_short Transtegumental diffusion of benzimidazole anthelmintics into Moniezia benedeni: correlation with their octanol–water partition coefficients
title_full Transtegumental diffusion of benzimidazole anthelmintics into Moniezia benedeni: correlation with their octanol–water partition coefficients
title_fullStr Transtegumental diffusion of benzimidazole anthelmintics into Moniezia benedeni: correlation with their octanol–water partition coefficients
title_full_unstemmed Transtegumental diffusion of benzimidazole anthelmintics into Moniezia benedeni: correlation with their octanol–water partition coefficients
title_sort Transtegumental diffusion of benzimidazole anthelmintics into Moniezia benedeni: correlation with their octanol–water partition coefficients
dc.creator.none.fl_str_mv Mottier, Maria de Lourdes
Alvarez, Luis Ignacio
Pis, Ma. Alejandra
Lanusse, Carlos Edmundo
author Mottier, Maria de Lourdes
author_facet Mottier, Maria de Lourdes
Alvarez, Luis Ignacio
Pis, Ma. Alejandra
Lanusse, Carlos Edmundo
author_role author
author2 Alvarez, Luis Ignacio
Pis, Ma. Alejandra
Lanusse, Carlos Edmundo
author2_role author
author
author
dc.subject.none.fl_str_mv BENZIMIDAZOLE
ANTHELMINTICS
MONIEZIA BENEDENI
topic BENZIMIDAZOLE
ANTHELMINTICS
MONIEZIA BENEDENI
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 experiments described here report on the correlation between the ex vivo diffusion of different benzimidazole (BZD) anthelmintics into the cestode parasite Moniezia benedeni, and their octanol–water partition coefficients (P.C.). The characterisation of the drug diffusion process into target parasites is relevant to understand the mechanism of drug penetration and the pharmacological activity of anthelmintic drugs. Specimens of the tapeworm M. benedeni, used as a helminth parasite model, were obtained from untreated cattle killed at the local abattoir. The collected parasites were incubated (5–210 min) with either fenbendazole (FBZ),albendazole (ABZ), ricobendazole (RBZ), oxfendazole (OFZ), mebendazole (MBZ), oxibendazole (OBZ), or thiabendazole (TBZ), in a Kreb’s Ringer Tris buffer medium at a final concentration of 5 nmol/ml. After the incubation time elapsed, samples of parasite material were chemically extracted and prepared for high performance liquid chromatography (HPLC) analysis to measure drug/metabolite concentrations. Additionally, the octanol–water P.C. for each molecule was estimated as an indicator of drug lipophilicity,using reversed phase HPLC analysis. All the incubated drugs were recovered from the tapeworms as early as 5 min post incubation. There was a high correlation (r ¼ 0:87) between drug lipophilicity, expressed as octanol–water P.C. (Log P), and drug availability within the parasite. The most lipophilic BZD compounds (FBZ, ABZ, and MBZ), with P.C. values higher than 3.7, were measured at significative higher concentrations within the tapeworm compared to those drugs with the lowest P.C. values. Considering the results from the current and previous studies, it is clear that passive diffusion is a major mechanism of BZD penetration into cestode parasites, where lipid solubility is a determinant factor influencing the diffusion of these anthelmintic molecules through the parasite tegument.
Fil: Mottier, Maria de Lourdes. 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: Alvarez, Luis Ignacio. 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: Pis, Ma. Alejandra. 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. 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
description The experiments described here report on the correlation between the ex vivo diffusion of different benzimidazole (BZD) anthelmintics into the cestode parasite Moniezia benedeni, and their octanol–water partition coefficients (P.C.). The characterisation of the drug diffusion process into target parasites is relevant to understand the mechanism of drug penetration and the pharmacological activity of anthelmintic drugs. Specimens of the tapeworm M. benedeni, used as a helminth parasite model, were obtained from untreated cattle killed at the local abattoir. The collected parasites were incubated (5–210 min) with either fenbendazole (FBZ),albendazole (ABZ), ricobendazole (RBZ), oxfendazole (OFZ), mebendazole (MBZ), oxibendazole (OBZ), or thiabendazole (TBZ), in a Kreb’s Ringer Tris buffer medium at a final concentration of 5 nmol/ml. After the incubation time elapsed, samples of parasite material were chemically extracted and prepared for high performance liquid chromatography (HPLC) analysis to measure drug/metabolite concentrations. Additionally, the octanol–water P.C. for each molecule was estimated as an indicator of drug lipophilicity,using reversed phase HPLC analysis. All the incubated drugs were recovered from the tapeworms as early as 5 min post incubation. There was a high correlation (r ¼ 0:87) between drug lipophilicity, expressed as octanol–water P.C. (Log P), and drug availability within the parasite. The most lipophilic BZD compounds (FBZ, ABZ, and MBZ), with P.C. values higher than 3.7, were measured at significative higher concentrations within the tapeworm compared to those drugs with the lowest P.C. values. Considering the results from the current and previous studies, it is clear that passive diffusion is a major mechanism of BZD penetration into cestode parasites, where lipid solubility is a determinant factor influencing the diffusion of these anthelmintic molecules through the parasite tegument.
publishDate 2003
dc.date.none.fl_str_mv 2003-01
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/11336/106799
Mottier, Maria de Lourdes; Alvarez, Luis Ignacio; Pis, Ma. Alejandra; Lanusse, Carlos Edmundo; Transtegumental diffusion of benzimidazole anthelmintics into Moniezia benedeni: correlation with their octanol–water partition coefficients; Academic Press Inc Elsevier Science; Experimental Parasitology; 103; 1-2; 1-2003; 1-7
0014-4894
1090-2449
CONICET Digital
CONICET
url http://hdl.handle.net/11336/106799
identifier_str_mv Mottier, Maria de Lourdes; Alvarez, Luis Ignacio; Pis, Ma. Alejandra; Lanusse, Carlos Edmundo; Transtegumental diffusion of benzimidazole anthelmintics into Moniezia benedeni: correlation with their octanol–water partition coefficients; Academic Press Inc Elsevier Science; Experimental Parasitology; 103; 1-2; 1-2003; 1-7
0014-4894
1090-2449
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1016/S0014-4894(03)00060-2
info:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/abs/pii/S0014489403000602
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 Academic Press Inc Elsevier Science
publisher.none.fl_str_mv Academic Press Inc Elsevier Science
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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score 13.070432

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