| Autor: |
Laeer S; Institute of Clinical Pharmacy and Pharmacotherapy, Heinrich-Heine-Universitaet Düsseldorf, 40225 Duesseldorf, Germany., Cawello W; Institute of Clinical Pharmacy and Pharmacotherapy, Heinrich-Heine-Universitaet Düsseldorf, 40225 Duesseldorf, Germany., Burckhardt BB; Institute of Clinical Pharmacy and Pharmacotherapy, Heinrich-Heine-Universitaet Düsseldorf, 40225 Duesseldorf, Germany., Ablonczy L; Goettsegen György Hungarian Institute of Cardiology (HPHC), 1450 Budapest, Hungary., Bajcetic M; Univerzitetska Dečja Klinika (UDK), University Children Hospital, School of Medicine, University of Belgrade, 11129 Belgrade, Serbia., Breur JMPJ; University Medical Center Utrecht, Wilhelmina Children's Hospital, 3584 CX Utrecht, The Netherlands., Dalinghaus M; Division of Pediatric Cardiology, Erasmus MC Sophia Children's Hospital, 3000 CA Rotterdam, The Netherlands., Male C; Department of Paediatrics and Adolescent Medicine, Medical University of Vienna, 1090 Vienna, Austria., de Wildt SN; Intensive Care and Department of Pediatric Surgery, Erasmus MC Sophia Children's Hospital, 3015 GJ Rotterdam, The Netherlands.; Department of Pharmacology and Toxicology, Radboud Institute of Health Sciences, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands., Breitkreutz J; Ethicare GmbH, 45721 Haltern am See, Germany., Faisal M; Institute of Clinical Pharmacy and Pharmacotherapy, Heinrich-Heine-Universitaet Düsseldorf, 40225 Duesseldorf, Germany., Keatley-Clarke A; The Children's Heart Federation, London EC2A 3NW, UK., Klingmann I; Pharmaplex Bvba, B-1970 Wezembeek-Oppem, Belgium., Lagler FB; Paracelsus Medizinische Privatuniversität, 5020 Salzburg, Austria. |
| Abstrakt: |
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. |
