Pharmacokinetic Characterization and Comparative Bioavailability of an Innovative Orodispersible Fixed-Dose Combination of Ivermectin and Albendazole: A Single Dose, Open Label, Se...

Autores
Algorta, Jaime; Krolewiecki, Alejandro Javier; Pinto, F.; Gold, S.; Muñoz, Jose
Año de publicación
2022
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Soil-transmitted helminths are intestinal worm diseases transmitted through the soil.Available treatments are albendazole and/or ivermectin. The co-administration ofexisting drugs is an appropriate strategy. A fixed-dose combination adds practicaladvantages mainly considering mass drug administration. The aim is to characterizepharmacokinetics and to evaluate the comparative bioavailability of an innovative fixeddosecombination of ivermectin/albendazole 18/400 mg compared with the marketedreferences. Seventy-eight healthy volunteers were included in this laboratory-blinded,randomized, three-treatment, three-period crossover study. Each subject received asingle dose of ivermectin/albendazole 18/400 mg (1 tablet); ivermectin 3mg (6 tablets);and albendazole 400 mg (1 tablet). Serial blood samples for the pharmacokinetic analysiswere obtained pre-dose and up to 72 h post-dose. Plasma concentrations of ivermectinH2B1a, ivermectin H2B1b, albendazole, and albendazole sulfoxide were analyzed by LCMS/MS. Pharmacokinetic parameters were estimated by a non-compartmental analysisand bioavailability compared through a bioequivalence analysis. Safety and tolerabilitywere assessed throughout the study. Main pharmacokinetic parameters of the fixedcombination were estimated for both, ivermectin [Cmax (mean, confidence interval): 86.40(30.42–39.23) ng/ml; AUC0-72 (mean, CI): 1,040 (530–1,678) ng·h/mL; tmax (median, min.,and max.); 4.50 (2.50–5.50)] and albendazole [Cmax (mean, CI): 22.27 (1.89–111.78) ng/ml; AUC0-72 (mean, CI): 94.65 (11.65–507.78) ng·h/mL; tmax (median, min., and max.):2.50 (1.00–12.00) h]. The 90% confidence interval of the geometric mean ratiosdemonstrated the bioequivalence in the case of ivermectin (Cmax: 110.68%–120.49%;AUC0-72: 110.46%–119.60%) but not in the case of albendazole (Cmax: 53.10%–70.34%;AUC0-72: 61.13%–76.54%). The pharmacokinetic profile of a new fixed-dose combinationof ivermectin and albendazole was characterized. The bioequivalence versus the referenceivermectin was demonstrated, though bioequivalence versus albendazole was not shown.The three medications analyzed were well tolerated. The results allow the advancement tothe next phase of the clinical program to demonstrate efficacy and safety in patientsaffected by soil-transmitted helminths.
Fil: Algorta, Jaime. No especifíca;
Fil: Krolewiecki, Alejandro Javier. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Pinto, F.. Hospital de Prelada; Portugal
Fil: Gold, S.. Fundación Mundo Sano; Argentina
Fil: Muñoz, Jose. Universidad de Barcelona; España
Materia
PHARMACOKINETICS
BIOAVAILABILITY
IVERMECTIN
ALBENDAZOLE
HELMINTHIASES
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:11336/243754

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network_name_str CONICET Digital (CONICET)
spelling Pharmacokinetic Characterization and Comparative Bioavailability of an Innovative Orodispersible Fixed-Dose Combination of Ivermectin and Albendazole: A Single Dose, Open Label, Sequence Randomized, Crossover Clinical Trial in Healthy VolunteersAlgorta, JaimeKrolewiecki, Alejandro JavierPinto, F.Gold, S.Muñoz, JosePHARMACOKINETICSBIOAVAILABILITYIVERMECTINALBENDAZOLEHELMINTHIASEShttps://purl.org/becyt/ford/3.3https://purl.org/becyt/ford/3Soil-transmitted helminths are intestinal worm diseases transmitted through the soil.Available treatments are albendazole and/or ivermectin. The co-administration ofexisting drugs is an appropriate strategy. A fixed-dose combination adds practicaladvantages mainly considering mass drug administration. The aim is to characterizepharmacokinetics and to evaluate the comparative bioavailability of an innovative fixeddosecombination of ivermectin/albendazole 18/400 mg compared with the marketedreferences. Seventy-eight healthy volunteers were included in this laboratory-blinded,randomized, three-treatment, three-period crossover study. Each subject received asingle dose of ivermectin/albendazole 18/400 mg (1 tablet); ivermectin 3mg (6 tablets);and albendazole 400 mg (1 tablet). Serial blood samples for the pharmacokinetic analysiswere obtained pre-dose and up to 72 h post-dose. Plasma concentrations of ivermectinH2B1a, ivermectin H2B1b, albendazole, and albendazole sulfoxide were analyzed by LCMS/MS. Pharmacokinetic parameters were estimated by a non-compartmental analysisand bioavailability compared through a bioequivalence analysis. Safety and tolerabilitywere assessed throughout the study. Main pharmacokinetic parameters of the fixedcombination were estimated for both, ivermectin [Cmax (mean, confidence interval): 86.40(30.42–39.23) ng/ml; AUC0-72 (mean, CI): 1,040 (530–1,678) ng·h/mL; tmax (median, min.,and max.); 4.50 (2.50–5.50)] and albendazole [Cmax (mean, CI): 22.27 (1.89–111.78) ng/ml; AUC0-72 (mean, CI): 94.65 (11.65–507.78) ng·h/mL; tmax (median, min., and max.):2.50 (1.00–12.00) h]. The 90% confidence interval of the geometric mean ratiosdemonstrated the bioequivalence in the case of ivermectin (Cmax: 110.68%–120.49%;AUC0-72: 110.46%–119.60%) but not in the case of albendazole (Cmax: 53.10%–70.34%;AUC0-72: 61.13%–76.54%). The pharmacokinetic profile of a new fixed-dose combinationof ivermectin and albendazole was characterized. The bioequivalence versus the referenceivermectin was demonstrated, though bioequivalence versus albendazole was not shown.The three medications analyzed were well tolerated. The results allow the advancement tothe next phase of the clinical program to demonstrate efficacy and safety in patientsaffected by soil-transmitted helminths.Fil: Algorta, Jaime. No especifíca;Fil: Krolewiecki, Alejandro Javier. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Pinto, F.. Hospital de Prelada; PortugalFil: Gold, S.. Fundación Mundo Sano; ArgentinaFil: Muñoz, Jose. Universidad de Barcelona; EspañaFrontiers Media2022-07info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/243754Algorta, Jaime; Krolewiecki, Alejandro Javier; Pinto, F.; Gold, S.; Muñoz, Jose; Pharmacokinetic Characterization and Comparative Bioavailability of an Innovative Orodispersible Fixed-Dose Combination of Ivermectin and Albendazole: A Single Dose, Open Label, Sequence Randomized, Crossover Clinical Trial in Healthy Volunteers; Frontiers Media; Frontiers in Pharmacology; 13; 7-2022; 1-111663-9812CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.914886/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fphar.2022.914886info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-03T09:55:32Zoai:ri.conicet.gov.ar:11336/243754instacron: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:34982025-09-03 09:55:32.782CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Pharmacokinetic Characterization and Comparative Bioavailability of an Innovative Orodispersible Fixed-Dose Combination of Ivermectin and Albendazole: A Single Dose, Open Label, Sequence Randomized, Crossover Clinical Trial in Healthy Volunteers
title Pharmacokinetic Characterization and Comparative Bioavailability of an Innovative Orodispersible Fixed-Dose Combination of Ivermectin and Albendazole: A Single Dose, Open Label, Sequence Randomized, Crossover Clinical Trial in Healthy Volunteers
spellingShingle Pharmacokinetic Characterization and Comparative Bioavailability of an Innovative Orodispersible Fixed-Dose Combination of Ivermectin and Albendazole: A Single Dose, Open Label, Sequence Randomized, Crossover Clinical Trial in Healthy Volunteers
Algorta, Jaime
PHARMACOKINETICS
BIOAVAILABILITY
IVERMECTIN
ALBENDAZOLE
HELMINTHIASES
title_short Pharmacokinetic Characterization and Comparative Bioavailability of an Innovative Orodispersible Fixed-Dose Combination of Ivermectin and Albendazole: A Single Dose, Open Label, Sequence Randomized, Crossover Clinical Trial in Healthy Volunteers
title_full Pharmacokinetic Characterization and Comparative Bioavailability of an Innovative Orodispersible Fixed-Dose Combination of Ivermectin and Albendazole: A Single Dose, Open Label, Sequence Randomized, Crossover Clinical Trial in Healthy Volunteers
title_fullStr Pharmacokinetic Characterization and Comparative Bioavailability of an Innovative Orodispersible Fixed-Dose Combination of Ivermectin and Albendazole: A Single Dose, Open Label, Sequence Randomized, Crossover Clinical Trial in Healthy Volunteers
title_full_unstemmed Pharmacokinetic Characterization and Comparative Bioavailability of an Innovative Orodispersible Fixed-Dose Combination of Ivermectin and Albendazole: A Single Dose, Open Label, Sequence Randomized, Crossover Clinical Trial in Healthy Volunteers
title_sort Pharmacokinetic Characterization and Comparative Bioavailability of an Innovative Orodispersible Fixed-Dose Combination of Ivermectin and Albendazole: A Single Dose, Open Label, Sequence Randomized, Crossover Clinical Trial in Healthy Volunteers
dc.creator.none.fl_str_mv Algorta, Jaime
Krolewiecki, Alejandro Javier
Pinto, F.
Gold, S.
Muñoz, Jose
author Algorta, Jaime
author_facet Algorta, Jaime
Krolewiecki, Alejandro Javier
Pinto, F.
Gold, S.
Muñoz, Jose
author_role author
author2 Krolewiecki, Alejandro Javier
Pinto, F.
Gold, S.
Muñoz, Jose
author2_role author
author
author
author
dc.subject.none.fl_str_mv PHARMACOKINETICS
BIOAVAILABILITY
IVERMECTIN
ALBENDAZOLE
HELMINTHIASES
topic PHARMACOKINETICS
BIOAVAILABILITY
IVERMECTIN
ALBENDAZOLE
HELMINTHIASES
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.3
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Soil-transmitted helminths are intestinal worm diseases transmitted through the soil.Available treatments are albendazole and/or ivermectin. The co-administration ofexisting drugs is an appropriate strategy. A fixed-dose combination adds practicaladvantages mainly considering mass drug administration. The aim is to characterizepharmacokinetics and to evaluate the comparative bioavailability of an innovative fixeddosecombination of ivermectin/albendazole 18/400 mg compared with the marketedreferences. Seventy-eight healthy volunteers were included in this laboratory-blinded,randomized, three-treatment, three-period crossover study. Each subject received asingle dose of ivermectin/albendazole 18/400 mg (1 tablet); ivermectin 3mg (6 tablets);and albendazole 400 mg (1 tablet). Serial blood samples for the pharmacokinetic analysiswere obtained pre-dose and up to 72 h post-dose. Plasma concentrations of ivermectinH2B1a, ivermectin H2B1b, albendazole, and albendazole sulfoxide were analyzed by LCMS/MS. Pharmacokinetic parameters were estimated by a non-compartmental analysisand bioavailability compared through a bioequivalence analysis. Safety and tolerabilitywere assessed throughout the study. Main pharmacokinetic parameters of the fixedcombination were estimated for both, ivermectin [Cmax (mean, confidence interval): 86.40(30.42–39.23) ng/ml; AUC0-72 (mean, CI): 1,040 (530–1,678) ng·h/mL; tmax (median, min.,and max.); 4.50 (2.50–5.50)] and albendazole [Cmax (mean, CI): 22.27 (1.89–111.78) ng/ml; AUC0-72 (mean, CI): 94.65 (11.65–507.78) ng·h/mL; tmax (median, min., and max.):2.50 (1.00–12.00) h]. The 90% confidence interval of the geometric mean ratiosdemonstrated the bioequivalence in the case of ivermectin (Cmax: 110.68%–120.49%;AUC0-72: 110.46%–119.60%) but not in the case of albendazole (Cmax: 53.10%–70.34%;AUC0-72: 61.13%–76.54%). The pharmacokinetic profile of a new fixed-dose combinationof ivermectin and albendazole was characterized. The bioequivalence versus the referenceivermectin was demonstrated, though bioequivalence versus albendazole was not shown.The three medications analyzed were well tolerated. The results allow the advancement tothe next phase of the clinical program to demonstrate efficacy and safety in patientsaffected by soil-transmitted helminths.
Fil: Algorta, Jaime. No especifíca;
Fil: Krolewiecki, Alejandro Javier. Universidad Nacional de Salta. Sede Regional Orán. Instituto de Investigación de Enfermedades Tropicales; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Pinto, F.. Hospital de Prelada; Portugal
Fil: Gold, S.. Fundación Mundo Sano; Argentina
Fil: Muñoz, Jose. Universidad de Barcelona; España
description Soil-transmitted helminths are intestinal worm diseases transmitted through the soil.Available treatments are albendazole and/or ivermectin. The co-administration ofexisting drugs is an appropriate strategy. A fixed-dose combination adds practicaladvantages mainly considering mass drug administration. The aim is to characterizepharmacokinetics and to evaluate the comparative bioavailability of an innovative fixeddosecombination of ivermectin/albendazole 18/400 mg compared with the marketedreferences. Seventy-eight healthy volunteers were included in this laboratory-blinded,randomized, three-treatment, three-period crossover study. Each subject received asingle dose of ivermectin/albendazole 18/400 mg (1 tablet); ivermectin 3mg (6 tablets);and albendazole 400 mg (1 tablet). Serial blood samples for the pharmacokinetic analysiswere obtained pre-dose and up to 72 h post-dose. Plasma concentrations of ivermectinH2B1a, ivermectin H2B1b, albendazole, and albendazole sulfoxide were analyzed by LCMS/MS. Pharmacokinetic parameters were estimated by a non-compartmental analysisand bioavailability compared through a bioequivalence analysis. Safety and tolerabilitywere assessed throughout the study. Main pharmacokinetic parameters of the fixedcombination were estimated for both, ivermectin [Cmax (mean, confidence interval): 86.40(30.42–39.23) ng/ml; AUC0-72 (mean, CI): 1,040 (530–1,678) ng·h/mL; tmax (median, min.,and max.); 4.50 (2.50–5.50)] and albendazole [Cmax (mean, CI): 22.27 (1.89–111.78) ng/ml; AUC0-72 (mean, CI): 94.65 (11.65–507.78) ng·h/mL; tmax (median, min., and max.):2.50 (1.00–12.00) h]. The 90% confidence interval of the geometric mean ratiosdemonstrated the bioequivalence in the case of ivermectin (Cmax: 110.68%–120.49%;AUC0-72: 110.46%–119.60%) but not in the case of albendazole (Cmax: 53.10%–70.34%;AUC0-72: 61.13%–76.54%). The pharmacokinetic profile of a new fixed-dose combinationof ivermectin and albendazole was characterized. The bioequivalence versus the referenceivermectin was demonstrated, though bioequivalence versus albendazole was not shown.The three medications analyzed were well tolerated. The results allow the advancement tothe next phase of the clinical program to demonstrate efficacy and safety in patientsaffected by soil-transmitted helminths.
publishDate 2022
dc.date.none.fl_str_mv 2022-07
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/11336/243754
Algorta, Jaime; Krolewiecki, Alejandro Javier; Pinto, F.; Gold, S.; Muñoz, Jose; Pharmacokinetic Characterization and Comparative Bioavailability of an Innovative Orodispersible Fixed-Dose Combination of Ivermectin and Albendazole: A Single Dose, Open Label, Sequence Randomized, Crossover Clinical Trial in Healthy Volunteers; Frontiers Media; Frontiers in Pharmacology; 13; 7-2022; 1-11
1663-9812
CONICET Digital
CONICET
url http://hdl.handle.net/11336/243754
identifier_str_mv Algorta, Jaime; Krolewiecki, Alejandro Javier; Pinto, F.; Gold, S.; Muñoz, Jose; Pharmacokinetic Characterization and Comparative Bioavailability of an Innovative Orodispersible Fixed-Dose Combination of Ivermectin and Albendazole: A Single Dose, Open Label, Sequence Randomized, Crossover Clinical Trial in Healthy Volunteers; Frontiers Media; Frontiers in Pharmacology; 13; 7-2022; 1-11
1663-9812
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://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2022.914886/full
info:eu-repo/semantics/altIdentifier/doi/10.3389/fphar.2022.914886
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 Frontiers Media
publisher.none.fl_str_mv Frontiers Media
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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