Muhammad Faisal1, Willi Cawello1, Stephanie Laeer1. 1. Institute of Clinical Pharmacy and Pharmacotherapy, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, Düsseldorf, Germany.
Abstract
Purpose: Enalapril has an established safety and efficacy in adults and is used in hypertension, heart failure, and renal failure. In pediatric patients, enalapril is labeled for children with hypertension and used off label in children with heart failure. The systematic literature search aims to assess the current knowledge about enalapril and its active metabolite enalaprilat pharmacokinetics in children as a basis for dose delineation for pediatric patients with heart failure. Methods: A systematic literature review was performed in the PubMed database using relevant keywords. Dose normalization of relevant pharmacokinetic parameters of the identified studies was done for comparison between different diseases and pediatric age groups. Results: The literature search has resulted in three pediatric pharmacokinetic studies of enalapril out of which Wells et al. reported about children with hypertension and Nakamura et al., and Llyod et al. presented data for pediatric heart failure patients. The area under the curve values of enalaprilat in hypertensive pediatric patients increased with respect to the age groups and showed maturation of body functions with increasing age. Dose normalized comparison with the heart failure studies revealed that although the pediatric heart failure patients of > 20 days of age showed the area under the curve a similar to that of hypertensive patients, two pediatric patients of very early age (<20 days) were presented with 5-6-fold higher area under the curve values. Conclusion: Data related to the pharmacokinetics of enalapril and enalaprilat in hypertensive patients and few data for young heart failure children are available. Comparison of dose normalized exposition of the active metabolite enalaprilat indicated similarities between heart failure and hypertensive patients and a potentially high exposition of premature patients but substantially more pharmacokinetic studies are required to have reliable and robust enalapril as well as enalaprilat exposures especially in pediatric patients with heart failure as a basis for any dose delineation.
Purpose: Enalapril has an established safety and efficacy in adults and is used in hypertension, heart failure, and renal failure. In pediatric patients, enalapril is labeled for children with hypertension and used off label in children with heart failure. The systematic literature search aims to assess the current knowledge about enalapril and its active metabolite enalaprilat pharmacokinetics in children as a basis for dose delineation for pediatric patients with heart failure. Methods: A systematic literature review was performed in the PubMed database using relevant keywords. Dose normalization of relevant pharmacokinetic parameters of the identified studies was done for comparison between different diseases and pediatric age groups. Results: The literature search has resulted in three pediatric pharmacokinetic studies of enalapril out of which Wells et al. reported about children with hypertension and Nakamura et al., and Llyod et al. presented data for pediatric heart failurepatients. The area under the curve values of enalaprilat in hypertensive pediatric patients increased with respect to the age groups and showed maturation of body functions with increasing age. Dose normalized comparison with the heart failure studies revealed that although the pediatric heart failurepatients of > 20 days of age showed the area under the curve a similar to that of hypertensivepatients, two pediatric patients of very early age (<20 days) were presented with 5-6-fold higher area under the curve values. Conclusion: Data related to the pharmacokinetics of enalapril and enalaprilat in hypertensivepatients and few data for young heart failurechildren are available. Comparison of dose normalized exposition of the active metabolite enalaprilat indicated similarities between heart failure and hypertensivepatients and a potentially high exposition of premature patients but substantially more pharmacokinetic studies are required to have reliable and robust enalapril as well as enalaprilat exposures especially in pediatric patients with heart failure as a basis for any dose delineation.
Authors: T Wells; R Rippley; R Hogg; A Sakarcan; D Blowey; P Walson; B Vogt; A Delucchi; M W Lo; E Hand; D Panebianco; W Shaw; S Shahinfar Journal: J Clin Pharmacol Date: 2001-10 Impact factor: 3.126
Authors: Pankaj K Sethi; Catherine A White; Brian S Cummings; Ronald N Hines; Srinivasa Muralidhara; James V Bruckner Journal: Pediatr Res Date: 2015-11-16 Impact factor: 3.756
Authors: E H Ulm; M Hichens; H J Gomez; A E Till; E Hand; T C Vassil; J Biollaz; H R Brunner; J L Schelling Journal: Br J Clin Pharmacol Date: 1982-09 Impact factor: 4.335
Authors: J G Cleland; H J Dargie; S G Ball; G Gillen; G P Hodsman; J J Morton; B W East; I Robertson; I Ford; J I Robertson Journal: Br Heart J Date: 1985-09
Authors: Milica Bajcetic; Saskia N de Wildt; Michiel Dalinghaus; Jörg Breitkreutz; Ingrid Klingmann; Florian B Lagler; Anne Keatley-Clarke; Johannes Mpj Breur; Christoph Male; Ida Jovanovic; Andras Szatmári; László Ablonczy; Bjoern B Burckhardt; Willi Cawello; Karl Kleine; Emina Obarcanin; Lucie Spatenkova; Vanessa Swoboda; Marijke van der Meulen; Peter Wagner; Jennifer Walsh; Stephanie Läer Journal: Contemp Clin Trials Commun Date: 2019-06-08
Authors: 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 Journal: Pharmaceutics Date: 2022-05-30 Impact factor: 6.525