TY - JOUR
T1 - 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)
AU - Laeer, Stephanie
AU - Cawello, Willi
AU - Burckhardt, Bjoern B.
AU - Ablonczy, László
AU - Bajcetic, Milica
AU - Breur, Johannes M.P.J.
AU - Dalinghaus, Michiel
AU - Male, Christoph
AU - de Wildt, Saskia N.
AU - Breitkreutz, Jörg
AU - Faisal, Muhammed
AU - Keatley-Clarke, Anne
AU - Klingmann, Ingrid
AU - Lagler, Florian B.
N1 - 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.
PY - 2022/5/30
Y1 - 2022/5/30
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85131715340&partnerID=8YFLogxK
U2 - 10.3390/pharmaceutics14061163
DO - 10.3390/pharmaceutics14061163
M3 - Article
AN - SCOPUS:85131715340
VL - 14
JO - Pharmaceutics
JF - Pharmaceutics
SN - 1999-4923
IS - 6
M1 - 1163
ER -