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)

Pharmaceutics

Christoph Male¹  Michiel Dalinghaus²  Jörg Breitkreutz³  László Ablonczy⁴  Bjoern B. Burckhardt⁵  Muhammed Faisal⁵  Willi Cawello⁵  Stephanie Laeer⁵  Saskia N. de Wildt⁶  Florian B. Lagler⁷  Ingrid Klingmann⁸  Anne Keatley-Clarke⁹  Johannes M. P. J. Breur^1,10  Milica Bajcetic^1,11 

[1] Department of Paediatrics and Adolescent Medicine, Medical University of Vienna, 1090 Vienna, Austria;Division of Pediatric Cardiology, Erasmus MC Sophia Children’s Hospital, 3000 CA Rotterdam, The Netherlands;Ethicare GmbH, 45721 Haltern am See, Germany;Goettsegen György Hungarian Institute of Cardiology (HPHC), 1450 Budapest, Hungary;Institute of Clinical Pharmacy and Pharmacotherapy, Heinrich-Heine-Universitaet Düsseldorf, 40225 Duesseldorf, Germany;Intensive Care and Department of Pediatric Surgery, Erasmus MC Sophia Children’s Hospital, 3015 GJ Rotterdam, The Netherlands;Paracelsus Medizinische Privatuniversität, 5020 Salzburg, Austria;Pharmaplex Bvba, B-1970 Wezembeek-Oppem, Belgium;The Children’s Heart Federation, London EC2A 3NW, UK;University Medical Center Utrecht, Wilhelmina Children’s Hospital, 3584 CX Utrecht, The Netherlands;Univerzitetska Dečja Klinika (UDK), University Children Hospital, School of Medicine, University of Belgrade, 11129 Belgrade, Serbia;

关键词: pediatric cardiology;    heart failure;    dilated cardiomyopathy;    congenital heart disease;    ACEIs;    enalapril;   

DOI  :  10.3390/pharmaceutics14061163

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown