Ivermectin systemic availability in adult volunteers treated with different oral pharmaceutical formulations

Autores
Ceballos, Laura; Alvarez, Luis Ignacio; Lifschitz, Adrian Luis; Lanusse, Carlos Edmundo
Año de publicación
2023
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Ivermectin (IVM) is currently approved as an antiparasitic agent for human use in the treatment of onchocerciasis, lymphatic filariasis, strongyloidiasis, scabies, and pediculosis. Recent findings indicate that IVM may reach other pharmacological targets, which accounts for its proven anti-inflammatory/immunomodulatory, cytostatic, and antiviral effects. However, little is known about the assessment of alternative drug formulations for human use. Objective: To compare the systemic availability and disposition kinetics of IVM orally administered as different pharmaceutical formulations (tablet, solution, or capsule) to healthy adults. Experimental design/main findings: Volunteers were randomly assigned to 1 of 3 experimental groups and orally treated with IVM as either, a tablet, solution, or capsules at 0.4 mg/kg in a three-phase crossover design. Blood samples were taken as dried blood spots (DBS) between 2 and 48 h post-treatment and IVM was analyzed by HPLC with fluorescence detection. IVM Cmax value was higher (P < 0.05) after the administration of the oral solution compared to treatments with both solid preparations. The oral solution resulted in a significantly higher IVM systemic exposure (AUC: 1653 ng h/mL) compared to the tablet (1056 ng h/mL) and capsule (996 ng h/mL) formulations. The simulation of a 5-day repeated administration for each formulation did not show a significant systemic accumulation. Conclusion: Beneficial effects against systemically located parasitic infections as well as in any other potential therapeutic field of IVM application would be expected from its use in the form of oral solution. This pharmacokinetic-based therapeutic advantage without the risk of excessive accumulation needs to be corroborated in clinical trials specifically designed for each purpose.
Fil: Ceballos, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina
Fil: Alvarez, Luis Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina
Fil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina
Fil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina
Materia
IVERMECTIN
ORAL PHARMACEUTICAL FORMULATION
SYSTEMIC EXPOSURE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/224994
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/224994
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Ivermectin systemic availability in adult volunteers treated with different oral pharmaceutical formulationsCeballos, LauraAlvarez, Luis IgnacioLifschitz, Adrian LuisLanusse, Carlos EdmundoIVERMECTINORAL PHARMACEUTICAL FORMULATIONSYSTEMIC EXPOSUREhttps://purl.org/becyt/ford/4.3https://purl.org/becyt/ford/4Ivermectin (IVM) is currently approved as an antiparasitic agent for human use in the treatment of onchocerciasis, lymphatic filariasis, strongyloidiasis, scabies, and pediculosis. Recent findings indicate that IVM may reach other pharmacological targets, which accounts for its proven anti-inflammatory/immunomodulatory, cytostatic, and antiviral effects. However, little is known about the assessment of alternative drug formulations for human use. Objective: To compare the systemic availability and disposition kinetics of IVM orally administered as different pharmaceutical formulations (tablet, solution, or capsule) to healthy adults. Experimental design/main findings: Volunteers were randomly assigned to 1 of 3 experimental groups and orally treated with IVM as either, a tablet, solution, or capsules at 0.4 mg/kg in a three-phase crossover design. Blood samples were taken as dried blood spots (DBS) between 2 and 48 h post-treatment and IVM was analyzed by HPLC with fluorescence detection. IVM Cmax value was higher (P < 0.05) after the administration of the oral solution compared to treatments with both solid preparations. The oral solution resulted in a significantly higher IVM systemic exposure (AUC: 1653 ng h/mL) compared to the tablet (1056 ng h/mL) and capsule (996 ng h/mL) formulations. The simulation of a 5-day repeated administration for each formulation did not show a significant systemic accumulation. Conclusion: Beneficial effects against systemically located parasitic infections as well as in any other potential therapeutic field of IVM application would be expected from its use in the form of oral solution. This pharmacokinetic-based therapeutic advantage without the risk of excessive accumulation needs to be corroborated in clinical trials specifically designed for each purpose.Fil: Ceballos, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; ArgentinaFil: Alvarez, Luis Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; ArgentinaFil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; ArgentinaFil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; ArgentinaElsevier France-Editions Scientifiques Medicales Elsevier2023-04info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/224994Ceballos, Laura; Alvarez, Luis Ignacio; Lifschitz, Adrian Luis; Lanusse, Carlos Edmundo; Ivermectin systemic availability in adult volunteers treated with different oral pharmaceutical formulations; Elsevier France-Editions Scientifiques Medicales Elsevier; Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie; 160; 4-2023; 1-70753-3322CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0753332223001798info:eu-repo/semantics/altIdentifier/doi/10.1016/j.biopha.2023.114391info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-nd/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-22T11:51:37Zoai:ri.conicet.gov.ar:11336/224994instacron: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:34982025-10-22 11:51:37.739CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Ivermectin systemic availability in adult volunteers treated with different oral pharmaceutical formulations
title Ivermectin systemic availability in adult volunteers treated with different oral pharmaceutical formulations
spellingShingle Ivermectin systemic availability in adult volunteers treated with different oral pharmaceutical formulations
Ceballos, Laura
IVERMECTIN
ORAL PHARMACEUTICAL FORMULATION
SYSTEMIC EXPOSURE
title_short Ivermectin systemic availability in adult volunteers treated with different oral pharmaceutical formulations
title_full Ivermectin systemic availability in adult volunteers treated with different oral pharmaceutical formulations
title_fullStr Ivermectin systemic availability in adult volunteers treated with different oral pharmaceutical formulations
title_full_unstemmed Ivermectin systemic availability in adult volunteers treated with different oral pharmaceutical formulations
title_sort Ivermectin systemic availability in adult volunteers treated with different oral pharmaceutical formulations
dc.creator.none.fl_str_mv Ceballos, Laura
Alvarez, Luis Ignacio
Lifschitz, Adrian Luis
Lanusse, Carlos Edmundo
author Ceballos, Laura
author_facet Ceballos, Laura
Alvarez, Luis Ignacio
Lifschitz, Adrian Luis
Lanusse, Carlos Edmundo
author_role author
author2 Alvarez, Luis Ignacio
Lifschitz, Adrian Luis
Lanusse, Carlos Edmundo
author2_role author
author
author
dc.subject.none.fl_str_mv IVERMECTIN
ORAL PHARMACEUTICAL FORMULATION
SYSTEMIC EXPOSURE
topic IVERMECTIN
ORAL PHARMACEUTICAL FORMULATION
SYSTEMIC EXPOSURE
purl_subject.fl_str_mv https://purl.org/becyt/ford/4.3
https://purl.org/becyt/ford/4
dc.description.none.fl_txt_mv Ivermectin (IVM) is currently approved as an antiparasitic agent for human use in the treatment of onchocerciasis, lymphatic filariasis, strongyloidiasis, scabies, and pediculosis. Recent findings indicate that IVM may reach other pharmacological targets, which accounts for its proven anti-inflammatory/immunomodulatory, cytostatic, and antiviral effects. However, little is known about the assessment of alternative drug formulations for human use. Objective: To compare the systemic availability and disposition kinetics of IVM orally administered as different pharmaceutical formulations (tablet, solution, or capsule) to healthy adults. Experimental design/main findings: Volunteers were randomly assigned to 1 of 3 experimental groups and orally treated with IVM as either, a tablet, solution, or capsules at 0.4 mg/kg in a three-phase crossover design. Blood samples were taken as dried blood spots (DBS) between 2 and 48 h post-treatment and IVM was analyzed by HPLC with fluorescence detection. IVM Cmax value was higher (P < 0.05) after the administration of the oral solution compared to treatments with both solid preparations. The oral solution resulted in a significantly higher IVM systemic exposure (AUC: 1653 ng h/mL) compared to the tablet (1056 ng h/mL) and capsule (996 ng h/mL) formulations. The simulation of a 5-day repeated administration for each formulation did not show a significant systemic accumulation. Conclusion: Beneficial effects against systemically located parasitic infections as well as in any other potential therapeutic field of IVM application would be expected from its use in the form of oral solution. This pharmacokinetic-based therapeutic advantage without the risk of excessive accumulation needs to be corroborated in clinical trials specifically designed for each purpose.
Fil: Ceballos, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina
Fil: Alvarez, Luis Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina
Fil: Lifschitz, Adrian Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina
Fil: Lanusse, Carlos Edmundo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Tandil. Centro de Investigación Veterinaria de Tandil. Universidad Nacional del Centro de la Provincia de Buenos Aires. Centro de Investigación Veterinaria de Tandil. Provincia de Buenos Aires. Gobernación. Comision de Investigaciones Científicas. Centro de Investigación Veterinaria de Tandil; Argentina. Universidad Nacional del Centro de la Provincia de Buenos Aires. Facultad de Ciencias Veterinarias; Argentina
description Ivermectin (IVM) is currently approved as an antiparasitic agent for human use in the treatment of onchocerciasis, lymphatic filariasis, strongyloidiasis, scabies, and pediculosis. Recent findings indicate that IVM may reach other pharmacological targets, which accounts for its proven anti-inflammatory/immunomodulatory, cytostatic, and antiviral effects. However, little is known about the assessment of alternative drug formulations for human use. Objective: To compare the systemic availability and disposition kinetics of IVM orally administered as different pharmaceutical formulations (tablet, solution, or capsule) to healthy adults. Experimental design/main findings: Volunteers were randomly assigned to 1 of 3 experimental groups and orally treated with IVM as either, a tablet, solution, or capsules at 0.4 mg/kg in a three-phase crossover design. Blood samples were taken as dried blood spots (DBS) between 2 and 48 h post-treatment and IVM was analyzed by HPLC with fluorescence detection. IVM Cmax value was higher (P < 0.05) after the administration of the oral solution compared to treatments with both solid preparations. The oral solution resulted in a significantly higher IVM systemic exposure (AUC: 1653 ng h/mL) compared to the tablet (1056 ng h/mL) and capsule (996 ng h/mL) formulations. The simulation of a 5-day repeated administration for each formulation did not show a significant systemic accumulation. Conclusion: Beneficial effects against systemically located parasitic infections as well as in any other potential therapeutic field of IVM application would be expected from its use in the form of oral solution. This pharmacokinetic-based therapeutic advantage without the risk of excessive accumulation needs to be corroborated in clinical trials specifically designed for each purpose.
publishDate 2023
dc.date.none.fl_str_mv 2023-04
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/11336/224994
Ceballos, Laura; Alvarez, Luis Ignacio; Lifschitz, Adrian Luis; Lanusse, Carlos Edmundo; Ivermectin systemic availability in adult volunteers treated with different oral pharmaceutical formulations; Elsevier France-Editions Scientifiques Medicales Elsevier; Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie; 160; 4-2023; 1-7
0753-3322
CONICET Digital
CONICET
url http://hdl.handle.net/11336/224994
identifier_str_mv Ceballos, Laura; Alvarez, Luis Ignacio; Lifschitz, Adrian Luis; Lanusse, Carlos Edmundo; Ivermectin systemic availability in adult volunteers treated with different oral pharmaceutical formulations; Elsevier France-Editions Scientifiques Medicales Elsevier; Biomedicine & Pharmacotherapy = Biomedecine & Pharmacotherapie; 160; 4-2023; 1-7
0753-3322
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://linkinghub.elsevier.com/retrieve/pii/S0753332223001798
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.biopha.2023.114391
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier France-Editions Scientifiques Medicales Elsevier
publisher.none.fl_str_mv Elsevier France-Editions Scientifiques Medicales Elsevier
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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