Clinical Pharmacology of Enalapril and Enalaprilat in Infants and Children - Abstract
Enalapril maleate is a prodrug that is hydrolysed by esterase to produce enalaprilat which is a potent inhibitor of the angiotensin-converting enzyme. Enalapril maleate is administered orally, the oral bioavailability is about 60%, whereas enalaprilat is administered intravenously, and both drugs are eliminated by renal route. The initial oral dose of enalapril is 40 µg/kg once-daily in infants and in children the initial oral dose is 2.5 mg once-daily. Enalapril controls the heart disease, restores ventricle physiology, and lowers blood pressure in infants and children. Enalapril is effective for congestive heart failure, for the chronic heart failure, and reduces pulmonary resistance. The elimination half-life of enalapril is about 10 hours in infants aged < 20 days and about 3 hours in older infants and children. Enalapril interacts with felodipine, metformin, and rifampicin and the co-administration of enalapril with furosemide causes acute kidney injury. Enalapril treats severe heart failure, a dose of 0.01 mg/kg of enalapril has been recommended in preterm infants, and enalapril lowers the diastolic blood pressure. Enalapril crosses the human placenta in-vivo but a study performed with the perfusion of the placenta reveals that enalaprilat does not equilibrate between the maternal and foetal comportments and enalaprilat poorly migrates into the breast-milk. The aim of this study is the review the published data on the enalapril dosing, efficacy, safety, effects, pharmacokinetics, drug interaction and treatment in infants and children and the transfer across the human placenta and the migration into the breast-milk.