Biopharmaceutical Characteristics of Nifurtimox Tablets for Age- and Body Weight-Adjusted Dosing in Patients With Chagas Disease

Autores
Stass, Heino; Feleder, Ethel; Garcia Bournissen, Facundo; Nagelschmitz, Johannes; Weimann, Boris; Yerino, Gustavo; Altcheh, Jaime Marcelo
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Treatment of Chagas disease with nifurtimox requires age- and body weight-adjusted dosing, resulting in complex dosing instructions. Appropriate formulations are needed for precise and compliant dosing, especially in pediatric patients. We characterized the biopharmaceutical features of a standard nifurtimox 120-mg tablet and a 30-mg tablet developed to improve dose accuracy. Two open-label, randomized crossover studies were conducted in adult outpatients with Chagas disease. One study investigated whether 4 × 30-mg tablets and 1 × 120-mg tablet were bioequivalent and whether tablets can be administered as an aqueous slurry without affecting bioavailability. The second study investigated the effect of a high-calorie/high-fat diet versus fasting on the absorption of nifurtimox after a single 4 × 30-mg dose. Interventions were equivalent if the 90% confidence interval (CI) of their least-squares (LS) mean ratios for both AUC0-tlast and Cmax were in the range of 80%-125%. The 4 × 30-mg and 1 × 120-mg tablet doses were bioequivalent (AUC0-tlast: LS mean ratio, 104.7%; 90%CI, 99.1%-110.7%; Cmax: LS mean ratio, 101.7%; 90%CI, 89.4%-115.6%; n = 24). Exposure when giving the 4 × 30-mg dose as a slurry or as tablets was comparable, with an AUC0-tlast ratio of 93.2% (84.2%-103.1%; n = 12) and a slightly decreased Cmax ratio for the slurry of 76.5% (68.8%-85.1%). Food improved the bioavailability of nifurtimox substantially (AUC0-tlast ratiofed/fasted, 172%; 90%CI, 154%-192%; Cmax ratiofed/fasted, 168%; 90%CI, 150%-187%). The data indicate that the 30- and 120-mg tablets are suitable for dosing adult and pediatric patients accurately; nifurtimox should be administered under fed conditions.
Fil: Stass, Heino. No especifíca;
Fil: Feleder, Ethel. No especifíca;
Fil: Garcia Bournissen, Facundo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina
Fil: Nagelschmitz, Johannes. No especifíca;
Fil: Weimann, Boris. No especifíca;
Fil: Yerino, Gustavo. No especifíca;
Fil: Altcheh, Jaime Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina
Materia
BIOAVAILABILITY
EXPOSURE
FASTING
FOOD EFFECT
TRYPANOSOMA CRUZI
WATER DISPERSIBLE
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/141095

id CONICETDig_084660fe9ac98908aa8587c763562ea0
oai_identifier_str oai:ri.conicet.gov.ar:11336/141095
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Biopharmaceutical Characteristics of Nifurtimox Tablets for Age- and Body Weight-Adjusted Dosing in Patients With Chagas DiseaseStass, HeinoFeleder, EthelGarcia Bournissen, FacundoNagelschmitz, JohannesWeimann, BorisYerino, GustavoAltcheh, Jaime MarceloBIOAVAILABILITYEXPOSUREFASTINGFOOD EFFECTTRYPANOSOMA CRUZIWATER DISPERSIBLEhttps://purl.org/becyt/ford/3.2https://purl.org/becyt/ford/3Treatment of Chagas disease with nifurtimox requires age- and body weight-adjusted dosing, resulting in complex dosing instructions. Appropriate formulations are needed for precise and compliant dosing, especially in pediatric patients. We characterized the biopharmaceutical features of a standard nifurtimox 120-mg tablet and a 30-mg tablet developed to improve dose accuracy. Two open-label, randomized crossover studies were conducted in adult outpatients with Chagas disease. One study investigated whether 4 × 30-mg tablets and 1 × 120-mg tablet were bioequivalent and whether tablets can be administered as an aqueous slurry without affecting bioavailability. The second study investigated the effect of a high-calorie/high-fat diet versus fasting on the absorption of nifurtimox after a single 4 × 30-mg dose. Interventions were equivalent if the 90% confidence interval (CI) of their least-squares (LS) mean ratios for both AUC0-tlast and Cmax were in the range of 80%-125%. The 4 × 30-mg and 1 × 120-mg tablet doses were bioequivalent (AUC0-tlast: LS mean ratio, 104.7%; 90%CI, 99.1%-110.7%; Cmax: LS mean ratio, 101.7%; 90%CI, 89.4%-115.6%; n = 24). Exposure when giving the 4 × 30-mg dose as a slurry or as tablets was comparable, with an AUC0-tlast ratio of 93.2% (84.2%-103.1%; n = 12) and a slightly decreased Cmax ratio for the slurry of 76.5% (68.8%-85.1%). Food improved the bioavailability of nifurtimox substantially (AUC0-tlast ratiofed/fasted, 172%; 90%CI, 154%-192%; Cmax ratiofed/fasted, 168%; 90%CI, 150%-187%). The data indicate that the 30- and 120-mg tablets are suitable for dosing adult and pediatric patients accurately; nifurtimox should be administered under fed conditions.Fil: Stass, Heino. No especifíca;Fil: Feleder, Ethel. No especifíca;Fil: Garcia Bournissen, Facundo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaFil: Nagelschmitz, Johannes. No especifíca;Fil: Weimann, Boris. No especifíca;Fil: Yerino, Gustavo. No especifíca;Fil: Altcheh, Jaime Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; ArgentinaBlackwell Publishing2020-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/141095Stass, Heino; Feleder, Ethel; Garcia Bournissen, Facundo; Nagelschmitz, Johannes; Weimann, Boris; et al.; Biopharmaceutical Characteristics of Nifurtimox Tablets for Age- and Body Weight-Adjusted Dosing in Patients With Chagas Disease; Blackwell Publishing; Clinical Pharmacology in Drug Development; 10; 5; 10-2020; 542-5552160-7648CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1002/cpdd.871info:eu-repo/semantics/altIdentifier/url/https://accp1.onlinelibrary.wiley.com/doi/10.1002/cpdd.871info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:48:46Zoai:ri.conicet.gov.ar:11336/141095instacron: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 09:48:46.907CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Biopharmaceutical Characteristics of Nifurtimox Tablets for Age- and Body Weight-Adjusted Dosing in Patients With Chagas Disease
title Biopharmaceutical Characteristics of Nifurtimox Tablets for Age- and Body Weight-Adjusted Dosing in Patients With Chagas Disease
spellingShingle Biopharmaceutical Characteristics of Nifurtimox Tablets for Age- and Body Weight-Adjusted Dosing in Patients With Chagas Disease
Stass, Heino
BIOAVAILABILITY
EXPOSURE
FASTING
FOOD EFFECT
TRYPANOSOMA CRUZI
WATER DISPERSIBLE
title_short Biopharmaceutical Characteristics of Nifurtimox Tablets for Age- and Body Weight-Adjusted Dosing in Patients With Chagas Disease
title_full Biopharmaceutical Characteristics of Nifurtimox Tablets for Age- and Body Weight-Adjusted Dosing in Patients With Chagas Disease
title_fullStr Biopharmaceutical Characteristics of Nifurtimox Tablets for Age- and Body Weight-Adjusted Dosing in Patients With Chagas Disease
title_full_unstemmed Biopharmaceutical Characteristics of Nifurtimox Tablets for Age- and Body Weight-Adjusted Dosing in Patients With Chagas Disease
title_sort Biopharmaceutical Characteristics of Nifurtimox Tablets for Age- and Body Weight-Adjusted Dosing in Patients With Chagas Disease
dc.creator.none.fl_str_mv Stass, Heino
Feleder, Ethel
Garcia Bournissen, Facundo
Nagelschmitz, Johannes
Weimann, Boris
Yerino, Gustavo
Altcheh, Jaime Marcelo
author Stass, Heino
author_facet Stass, Heino
Feleder, Ethel
Garcia Bournissen, Facundo
Nagelschmitz, Johannes
Weimann, Boris
Yerino, Gustavo
Altcheh, Jaime Marcelo
author_role author
author2 Feleder, Ethel
Garcia Bournissen, Facundo
Nagelschmitz, Johannes
Weimann, Boris
Yerino, Gustavo
Altcheh, Jaime Marcelo
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv BIOAVAILABILITY
EXPOSURE
FASTING
FOOD EFFECT
TRYPANOSOMA CRUZI
WATER DISPERSIBLE
topic BIOAVAILABILITY
EXPOSURE
FASTING
FOOD EFFECT
TRYPANOSOMA CRUZI
WATER DISPERSIBLE
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.2
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Treatment of Chagas disease with nifurtimox requires age- and body weight-adjusted dosing, resulting in complex dosing instructions. Appropriate formulations are needed for precise and compliant dosing, especially in pediatric patients. We characterized the biopharmaceutical features of a standard nifurtimox 120-mg tablet and a 30-mg tablet developed to improve dose accuracy. Two open-label, randomized crossover studies were conducted in adult outpatients with Chagas disease. One study investigated whether 4 × 30-mg tablets and 1 × 120-mg tablet were bioequivalent and whether tablets can be administered as an aqueous slurry without affecting bioavailability. The second study investigated the effect of a high-calorie/high-fat diet versus fasting on the absorption of nifurtimox after a single 4 × 30-mg dose. Interventions were equivalent if the 90% confidence interval (CI) of their least-squares (LS) mean ratios for both AUC0-tlast and Cmax were in the range of 80%-125%. The 4 × 30-mg and 1 × 120-mg tablet doses were bioequivalent (AUC0-tlast: LS mean ratio, 104.7%; 90%CI, 99.1%-110.7%; Cmax: LS mean ratio, 101.7%; 90%CI, 89.4%-115.6%; n = 24). Exposure when giving the 4 × 30-mg dose as a slurry or as tablets was comparable, with an AUC0-tlast ratio of 93.2% (84.2%-103.1%; n = 12) and a slightly decreased Cmax ratio for the slurry of 76.5% (68.8%-85.1%). Food improved the bioavailability of nifurtimox substantially (AUC0-tlast ratiofed/fasted, 172%; 90%CI, 154%-192%; Cmax ratiofed/fasted, 168%; 90%CI, 150%-187%). The data indicate that the 30- and 120-mg tablets are suitable for dosing adult and pediatric patients accurately; nifurtimox should be administered under fed conditions.
Fil: Stass, Heino. No especifíca;
Fil: Feleder, Ethel. No especifíca;
Fil: Garcia Bournissen, Facundo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina
Fil: Nagelschmitz, Johannes. No especifíca;
Fil: Weimann, Boris. No especifíca;
Fil: Yerino, Gustavo. No especifíca;
Fil: Altcheh, Jaime Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Niños "Ricardo Gutiérrez"; Argentina. Gobierno de la Ciudad de Buenos Aires. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto Multidisciplinario de Investigaciones en Patologías Pediátricas; Argentina
description Treatment of Chagas disease with nifurtimox requires age- and body weight-adjusted dosing, resulting in complex dosing instructions. Appropriate formulations are needed for precise and compliant dosing, especially in pediatric patients. We characterized the biopharmaceutical features of a standard nifurtimox 120-mg tablet and a 30-mg tablet developed to improve dose accuracy. Two open-label, randomized crossover studies were conducted in adult outpatients with Chagas disease. One study investigated whether 4 × 30-mg tablets and 1 × 120-mg tablet were bioequivalent and whether tablets can be administered as an aqueous slurry without affecting bioavailability. The second study investigated the effect of a high-calorie/high-fat diet versus fasting on the absorption of nifurtimox after a single 4 × 30-mg dose. Interventions were equivalent if the 90% confidence interval (CI) of their least-squares (LS) mean ratios for both AUC0-tlast and Cmax were in the range of 80%-125%. The 4 × 30-mg and 1 × 120-mg tablet doses were bioequivalent (AUC0-tlast: LS mean ratio, 104.7%; 90%CI, 99.1%-110.7%; Cmax: LS mean ratio, 101.7%; 90%CI, 89.4%-115.6%; n = 24). Exposure when giving the 4 × 30-mg dose as a slurry or as tablets was comparable, with an AUC0-tlast ratio of 93.2% (84.2%-103.1%; n = 12) and a slightly decreased Cmax ratio for the slurry of 76.5% (68.8%-85.1%). Food improved the bioavailability of nifurtimox substantially (AUC0-tlast ratiofed/fasted, 172%; 90%CI, 154%-192%; Cmax ratiofed/fasted, 168%; 90%CI, 150%-187%). The data indicate that the 30- and 120-mg tablets are suitable for dosing adult and pediatric patients accurately; nifurtimox should be administered under fed conditions.
publishDate 2020
dc.date.none.fl_str_mv 2020-10
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/11336/141095
Stass, Heino; Feleder, Ethel; Garcia Bournissen, Facundo; Nagelschmitz, Johannes; Weimann, Boris; et al.; Biopharmaceutical Characteristics of Nifurtimox Tablets for Age- and Body Weight-Adjusted Dosing in Patients With Chagas Disease; Blackwell Publishing; Clinical Pharmacology in Drug Development; 10; 5; 10-2020; 542-555
2160-7648
CONICET Digital
CONICET
url http://hdl.handle.net/11336/141095
identifier_str_mv Stass, Heino; Feleder, Ethel; Garcia Bournissen, Facundo; Nagelschmitz, Johannes; Weimann, Boris; et al.; Biopharmaceutical Characteristics of Nifurtimox Tablets for Age- and Body Weight-Adjusted Dosing in Patients With Chagas Disease; Blackwell Publishing; Clinical Pharmacology in Drug Development; 10; 5; 10-2020; 542-555
2160-7648
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1002/cpdd.871
info:eu-repo/semantics/altIdentifier/url/https://accp1.onlinelibrary.wiley.com/doi/10.1002/cpdd.871
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Blackwell Publishing
publisher.none.fl_str_mv Blackwell Publishing
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_ 1844613513176154112
score 13.070432