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.
Highlights
A pediatric population is a heterogeneous group with developmental differences in physiology, pathology, and biochemistry from birth until adolescence [1]
Information like study authors, study design, age groups, disease state, dose and dosage form administered, and pharmacokinetic parameters of each pediatric age group was noted in tabular form and these parameters were further discussed and compared to conclude the evidence related to exposure of enalapril and enalaprilat in pediatric patients
Data related to the pharmacokinetics of enalapril and enalaprilat in hypertensive patients and few data for young heart failure children are available
Summary
A pediatric population is a heterogeneous group with developmental differences in physiology, pathology, and biochemistry from birth until adolescence [1]. Due to these differences, the pediatric age groups are arbitrarily sub-classified into preterm newborn, newborn (0–28 days), infant (>28 days−12 months), toddler (>12 months−23 months), preschool child (2–5 years), school-age child (6–11 years), and adolescents (12–18 years) [2, 3]. Enalapril is an angiotensin-converting enzyme inhibitor drug [7] used in adult patients with hypertension [8], heart failure [9, 10], and renal failure [11] and has established safety and efficacy in adults. Angiotensin-converting enzyme inhibitors (ACE) are recommended in international guidelines for pediatric heart failure due to several published non-randomized controlled clinical trials suggesting effective and safe use in children of all age groups [15] and high level of evidence of improved heart failure prognosis in adult heart failure use [13]
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