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Enalapril and Enalaprilat Pharmacokinetics in Children with Heart Failure Due to Dilated Cardiomyopathy and Congestive Heart Failure after Administration of an Orodispersible Enalapril Minitablet (LENA-Studies)

Angiotensin-converting enzyme inhibitors (ACEI), such as enalapril, are a cornerstone of treatment for pediatric heart failure which is still used off-label. Using a novel age-appropriate formulation of enalapril orodispersible minitablets (ODMTs), phase II/III open-label, multicenter pharmacokineti...

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Autores principales: Laeer, Stephanie, Cawello, Willi, Burckhardt, Bjoern B., Ablonczy, László, Bajcetic, Milica, Breur, Johannes M. P. J., Dalinghaus, Michiel, Male, Christoph, de Wildt, Saskia N., Breitkreutz, Jörg, Faisal, Muhammed, Keatley-Clarke, Anne, Klingmann, Ingrid, Lagler, Florian B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9228797/
https://www.ncbi.nlm.nih.gov/pubmed/35745735
http://dx.doi.org/10.3390/pharmaceutics14061163
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author Laeer, Stephanie
Cawello, Willi
Burckhardt, Bjoern B.
Ablonczy, László
Bajcetic, Milica
Breur, Johannes M. P. J.
Dalinghaus, Michiel
Male, Christoph
de Wildt, Saskia N.
Breitkreutz, Jörg
Faisal, Muhammed
Keatley-Clarke, Anne
Klingmann, Ingrid
Lagler, Florian B.
author_facet Laeer, Stephanie
Cawello, Willi
Burckhardt, Bjoern B.
Ablonczy, László
Bajcetic, Milica
Breur, Johannes M. P. J.
Dalinghaus, Michiel
Male, Christoph
de Wildt, Saskia N.
Breitkreutz, Jörg
Faisal, Muhammed
Keatley-Clarke, Anne
Klingmann, Ingrid
Lagler, Florian B.
author_sort Laeer, Stephanie
collection PubMed
description Angiotensin-converting enzyme inhibitors (ACEI), such as enalapril, are a cornerstone of treatment for pediatric heart failure which is still used off-label. Using a novel age-appropriate formulation of enalapril orodispersible minitablets (ODMTs), phase II/III open-label, multicenter pharmacokinetic (PK) bridging studies were performed in pediatric patients with heart failure due to dilated cardiomyopathy (DCM) and congenital heart disease (CHD) in five participating European countries. Children were treated for 8 weeks with ODMTs according to an age-appropriate dosing schedule. The primary objective was to describe PK parameters (area under the curve (AUC), maximal concentration (Cmax), time to reach maximal concentration (t-max)) of enalapril and its active metabolite enalaprilat. Of 102 patients, 89 patients (n = 26, DCM; n = 63 CHD) were included in the primary PK endpoint analysis. Rate and extent of enalapril and its active metabolite enalaprilat were described and etiology and age could be identified as potential PK modifying factors. The dosing schedule appeared to be tolerated well and did not result in any significant drug-related serious adverse events. The PK analysis and the lack of severe safety events supports the applied age-appropriate dosing schedule for the enalapril ODMTs.
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spelling pubmed-92287972022-06-25 Enalapril and Enalaprilat Pharmacokinetics in Children with Heart Failure Due to Dilated Cardiomyopathy and Congestive Heart Failure after Administration of an Orodispersible Enalapril Minitablet (LENA-Studies) Laeer, Stephanie Cawello, Willi Burckhardt, Bjoern B. Ablonczy, László Bajcetic, Milica Breur, Johannes M. P. J. Dalinghaus, Michiel Male, Christoph de Wildt, Saskia N. Breitkreutz, Jörg Faisal, Muhammed Keatley-Clarke, Anne Klingmann, Ingrid Lagler, Florian B. Pharmaceutics Article Angiotensin-converting enzyme inhibitors (ACEI), such as enalapril, are a cornerstone of treatment for pediatric heart failure which is still used off-label. Using a novel age-appropriate formulation of enalapril orodispersible minitablets (ODMTs), phase II/III open-label, multicenter pharmacokinetic (PK) bridging studies were performed in pediatric patients with heart failure due to dilated cardiomyopathy (DCM) and congenital heart disease (CHD) in five participating European countries. Children were treated for 8 weeks with ODMTs according to an age-appropriate dosing schedule. The primary objective was to describe PK parameters (area under the curve (AUC), maximal concentration (Cmax), time to reach maximal concentration (t-max)) of enalapril and its active metabolite enalaprilat. Of 102 patients, 89 patients (n = 26, DCM; n = 63 CHD) were included in the primary PK endpoint analysis. Rate and extent of enalapril and its active metabolite enalaprilat were described and etiology and age could be identified as potential PK modifying factors. The dosing schedule appeared to be tolerated well and did not result in any significant drug-related serious adverse events. The PK analysis and the lack of severe safety events supports the applied age-appropriate dosing schedule for the enalapril ODMTs. MDPI 2022-05-30 /pmc/articles/PMC9228797/ /pubmed/35745735 http://dx.doi.org/10.3390/pharmaceutics14061163 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Laeer, Stephanie
Cawello, Willi
Burckhardt, Bjoern B.
Ablonczy, László
Bajcetic, Milica
Breur, Johannes M. P. J.
Dalinghaus, Michiel
Male, Christoph
de Wildt, Saskia N.
Breitkreutz, Jörg
Faisal, Muhammed
Keatley-Clarke, Anne
Klingmann, Ingrid
Lagler, Florian B.
Enalapril and Enalaprilat Pharmacokinetics in Children with Heart Failure Due to Dilated Cardiomyopathy and Congestive Heart Failure after Administration of an Orodispersible Enalapril Minitablet (LENA-Studies)
title Enalapril and Enalaprilat Pharmacokinetics in Children with Heart Failure Due to Dilated Cardiomyopathy and Congestive Heart Failure after Administration of an Orodispersible Enalapril Minitablet (LENA-Studies)
title_full Enalapril and Enalaprilat Pharmacokinetics in Children with Heart Failure Due to Dilated Cardiomyopathy and Congestive Heart Failure after Administration of an Orodispersible Enalapril Minitablet (LENA-Studies)
title_fullStr Enalapril and Enalaprilat Pharmacokinetics in Children with Heart Failure Due to Dilated Cardiomyopathy and Congestive Heart Failure after Administration of an Orodispersible Enalapril Minitablet (LENA-Studies)
title_full_unstemmed Enalapril and Enalaprilat Pharmacokinetics in Children with Heart Failure Due to Dilated Cardiomyopathy and Congestive Heart Failure after Administration of an Orodispersible Enalapril Minitablet (LENA-Studies)
title_short Enalapril and Enalaprilat Pharmacokinetics in Children with Heart Failure Due to Dilated Cardiomyopathy and Congestive Heart Failure after Administration of an Orodispersible Enalapril Minitablet (LENA-Studies)
title_sort enalapril and enalaprilat pharmacokinetics in children with heart failure due to dilated cardiomyopathy and congestive heart failure after administration of an orodispersible enalapril minitablet (lena-studies)
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9228797/
https://www.ncbi.nlm.nih.gov/pubmed/35745735
http://dx.doi.org/10.3390/pharmaceutics14061163
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