Faisal Muhammad, Cawello Willi, Laeer Stephanie
Institute of Clinical Pharmacy and Pharmacotherapy, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, Düsseldorf, Germany.
Front Pediatr. 2021 Feb 12;9:611322. doi: 10.3389/fped.2021.611322. eCollection 2021.
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. 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. 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. 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.
依那普利在成人中具有既定的安全性和有效性，用于治疗高血压、心力衰竭和肾衰竭。在儿科患者中，依那普利被批准用于治疗高血压儿童，也可用于治疗心力衰竭儿童（属超说明书用药）。本系统文献检索旨在评估目前关于依那普利及其活性代谢产物依那普利拉在儿童体内药代动力学的知识，为心力衰竭儿科患者的剂量确定提供依据。使用相关关键词在PubMed数据库中进行了系统文献综述。对已识别研究的相关药代动力学参数进行剂量标准化，以便在不同疾病和儿科年龄组之间进行比较。文献检索得到了三项关于依那普利的儿科药代动力学研究，其中Wells等人报告了高血压儿童的情况，Nakamura等人和Llyod等人提供了儿科心力衰竭患者的数据。高血压儿科患者中依那普利拉的曲线下面积值随年龄组增加而增加，表明身体功能随年龄增长而成熟。与心力衰竭研究的剂量标准化比较显示，虽然年龄大于20天的儿科心力衰竭患者的曲线下面积与高血压患者相似，但两名极年幼（<20天）的儿科患者的曲线下面积值高出5 - 6倍。有关于依那普利和依那普利拉在高血压患者中的药代动力学数据，而关于年幼心力衰竭儿童的数据较少。活性代谢产物依那普利拉的剂量标准化暴露比较表明，心力衰竭患者和高血压患者之间存在相似性，早产儿可能有较高的暴露，但需要更多的药代动力学研究来获得可靠和稳健的依那普利以及依那普利拉暴露数据，尤其是在心力衰竭儿科患者中，作为任何剂量确定的基础。
