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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/243754
Ver los metadatos del registro completo
id |
CONICETDig_cd9ca047b566b920f76761a57be8e250 |
---|---|
oai_identifier_str |
oai:ri.conicet.gov.ar:11336/243754 |
network_acronym_str |
CONICETDig |
repository_id_str |
3498 |
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 |
_version_ |
1842269350971572224 |
score |
13.13397 |