The Pharmacokinetics of Enalapril in Children and Infants with Hypertension

Abstract

Forty children with hypertension between the age of 2 months and 15 years received 0.07 to 0.14 mg/kg of enalapril as a single daily dose. Enalapril was administered orally as a novel extemporaneous suspension in children younger than 6 years of age and as tablets in older children. First-dose and steady-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 serum concentrations for enalapril occurred approximately 1 hour after administration. Serum concentrations of enalaprilat, the active metabolite of enalapril, 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. Based 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 percentage conversion of enalapril to enalaprilat ranged from 64.7% for children ages 1 to 24 months to 74.6% for children ages 6 to < 12 years. The median 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 enalapril or resulted in discontinuation of the study drug. The extemporaneous suspension used in this study was tolerated well. The pharmacokinetics of enalapril and enalaprilat in hypertensive children ages 2 months to 15 years with normal renal function appears to be similar to that previously observed in healthy adults.

Manejo de la hipertensión arterial en niños y adolescentes: recomendaciones de la Sociedad Europea de Hipertensión

“…Debido a ello, debe administrarse dos o tres veces al día, por lo que ha sido sustituido por IECA de acción prolongada 130 , algunos de los cuales se han estudiado recientemente en niños 120 . Por ejemplo, se dispone de resultados de eficacia controlados con placebo para enalapril 131 , fosinopril 132 y lisinopril 133 , y se han llevado a cabo estudios farmacocinéticos para enalapril 134 , lisinopril 135 y quinapril 136 . Si bien los estudios con enalapril 131 y lisinopril 133 han establecido una dosis efectiva mínima de 0,08 mg/kg/día, dosis de 0,6 mg/kg/día fueron bien toleradas.…”

A multicenter study of the pharmacokinetics of lisinopril in pediatric patients with hypertension

“…While recent reports have described the pharmacokinetics (PK) [5] and dose-response [6] to enalapril in children, similar studies have not been reported with lisinopril. There have been few reported adverse events from lisinopril in pediatric patients, and no clustering of specific adverse events has been observed in children.…”

Treatment of primary and secondary hypertension in children

“…The dose of enalapril in children has been reported in a few studies. Wells et al [25] did a comprehensive analysis of the pharmacokinetics of enalapril in children. They used a dosing schedule of 2.5 mg for children less than 28 kg of body weight and 5.0 mg for children greater than 28 kg of body weight, translating to a dosing range of 0.07-0.14 mg/kg.…”