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)

Stephanie Laeer*, Willi Cawello, Bjoern B. Burckhardt, László Ablonczy, Milica Bajcetic, Johannes M.P.J. Breur, Michiel Dalinghaus, Christoph Male, Saskia N. de Wildt, Jörg Breitkreutz, Muhammed Faisal, Anne Keatley-Clarke, Ingrid Klingmann, Florian B. Lagler

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

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.

Original languageEnglish
Article number1163
JournalPharmaceutics
Volume14
Issue number6
DOIs
Publication statusPublished - 30 May 2022

Bibliographical note

Funding Information:
Funding: The research work was a part of project LENA (labeling of enalapril from neonates up to adolescents) which is funded by a European Union Seventh Framework Program (FP7/2007-2013) under the grant agreement no 602295.

Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.

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