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.
Reference58 articles.
1. Committee for Proprietary Medicinal Products (CPMP) Summary Information of Referral Opinion Pursuant to Article 30 of Council Directive 2001/83/EC for Renitec and associated names (See Annex I), London 4 December 2003
https://www.ema.europa.eu/documents/referral/summary-information-referral-opinion-pursuant-article-30-council-directive-2001/83/ec-renitec-associated-names-see-annex-i-international-non-proprietary-name-inn-enalapril-background_en.pdf
2. Effects of enalapril in heart failure: a double blind study of effects on exercise performance, renal function, hormones, and metabolic state.
3. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to update the 2001 Guidelines for the Evaluation and Management of Heart Failure);Hunt;J. Am. Coll. Cardiol.,2005
4. Report on the Expert Group Meeting of Paediatric Heart Failure, London 29 November 2010
https://www.ema.europa.eu/documents/other/report-expert-group-meeting-paediatric-heart-failure-london-29-november-2010_en.pdf
5. Orally administered enalapril for infants with congestive heart failure: A dose-finding study
Cited by
3 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献