The pharmacokinetics of enalapril in children and infants with hypertension

Forty children with hypertension between the age of 2 months and 15 years r eceived 0.07 to 0.14 mg/kg of enalapril as a single daily dose. Enalapril w as administered orally as a novel extemporaneous suspension in children you nger than 6 years of age and as tablets in older children. First-dose and s teady-state pharmacokinetics were estimated in children ages 1 to 24 months , 25 months to < 6 years, 6 to < 12 years, and 12 to < 16 years. Maximum se rum concentrations for enalapril occurred approximately 1 hour after admini stration. Serum concentrations of enalaprilat, the active metabolite of ena lapril, peaked between 4 and 6 hours after the first dose and 3 and 4 hours after multiple doses. The area under the concentration versus time curve ( AUC), adjusted for body surface area, did not differ between age groups. Ba sed on comparison of first-dose and steady-state AUCs, the accumulation of enalaprilat in children ranged from 1.13- to 1.45-fold. For children ages 2 to 15 years, mean urinary recovery of total enalaprilat ranged from 58.3% in children ages 6 to < 12 years to 71.4% in children ages 12 to < 16 years . Urinary recovery for children ages 2 to < 6 years was 66.8%. The mean per centage conversion of enalapril to enalaprilat ranged from 64.7% for childr en ages 1 to 24 months to 74.6% for children ages 6 to < 12 years. The medi an effective half-life for accumulation ranged from 14.6 hours in children ages 12 to < 16 years to 16.3 hours in children ages 6 to < 12 years. There were two serious adverse events, neither of which was attributed to enalap ril or resulted in discontinuation of the study drug. The extemporaneous su spension used in this study was tolerated well. The pharmacokinetics of ena lapril and enalaprilat in hypertensive children ages 2 months to 15 years w ith normal renal function appears to be similar to that previously observed in healthy adults. (C) 2001 the American College of Clinical Pharmacology.