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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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/6/1163 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Stephanie Laeer |
| collection | DOAJ |
| 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 (<i>n</i> = 26, DCM; <i>n</i> = 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. |
| first_indexed | 2024-03-09T22:46:45Z |
| format | Article |
| id | doaj.art-b89dc3f16c3f4e7d9e7d6a9dfa33561e |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T22:46:45Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-b89dc3f16c3f4e7d9e7d6a9dfa33561e2023-11-23T18:29:15ZengMDPI AGPharmaceutics1999-49232022-05-01146116310.3390/pharmaceutics14061163Enalapril 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 Laeer0Willi Cawello1Bjoern B. Burckhardt2László Ablonczy3Milica Bajcetic4Johannes M. P. J. Breur5Michiel Dalinghaus6Christoph Male7Saskia N. de Wildt8Jörg Breitkreutz9Muhammed Faisal10Anne Keatley-Clarke11Ingrid Klingmann12Florian B. Lagler13Institute of Clinical Pharmacy and Pharmacotherapy, Heinrich-Heine-Universitaet Düsseldorf, 40225 Duesseldorf, GermanyInstitute of Clinical Pharmacy and Pharmacotherapy, Heinrich-Heine-Universitaet Düsseldorf, 40225 Duesseldorf, GermanyInstitute of Clinical Pharmacy and Pharmacotherapy, Heinrich-Heine-Universitaet Düsseldorf, 40225 Duesseldorf, GermanyGoettsegen György Hungarian Institute of Cardiology (HPHC), 1450 Budapest, HungaryUniverzitetska Dečja Klinika (UDK), University Children Hospital, School of Medicine, University of Belgrade, 11129 Belgrade, SerbiaUniversity Medical Center Utrecht, Wilhelmina Children’s Hospital, 3584 CX Utrecht, The NetherlandsDivision of Pediatric Cardiology, Erasmus MC Sophia Children’s Hospital, 3000 CA Rotterdam, The NetherlandsDepartment of Paediatrics and Adolescent Medicine, Medical University of Vienna, 1090 Vienna, AustriaIntensive Care and Department of Pediatric Surgery, Erasmus MC Sophia Children’s Hospital, 3015 GJ Rotterdam, The NetherlandsEthicare GmbH, 45721 Haltern am See, GermanyInstitute of Clinical Pharmacy and Pharmacotherapy, Heinrich-Heine-Universitaet Düsseldorf, 40225 Duesseldorf, GermanyThe Children’s Heart Federation, London EC2A 3NW, UKPharmaplex Bvba, B-1970 Wezembeek-Oppem, BelgiumParacelsus Medizinische Privatuniversität, 5020 Salzburg, AustriaAngiotensin-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 (<i>n</i> = 26, DCM; <i>n</i> = 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.https://www.mdpi.com/1999-4923/14/6/1163pediatric cardiologyheart failuredilated cardiomyopathycongenital heart diseaseACEIsenalapril |
| spellingShingle | 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 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 pediatric cardiology heart failure dilated cardiomyopathy congenital heart disease ACEIs enalapril |
| 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 | pediatric cardiology heart failure dilated cardiomyopathy congenital heart disease ACEIs enalapril |
| url | https://www.mdpi.com/1999-4923/14/6/1163 |
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