The pharmacokinetics of enalapril in children and infants with hypertension.
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.
Wells
T
T
University of Arkansas for Medical Sciences and Arkansas Children's Hospital, Little Rock 72202, USA.
Rippley
R
R
Hogg
R
R
Sakarcan
A
A
Blowey
D
D
Walson
P
P
Vogt
B
B
Delucchi
A
A
Lo
M W
MW
Hand
E
E
Panebianco
D
D
Shaw
W
W
Shahinfar
S
S
D000293:Adolescent; D000704:Analysis of Variance; D000959:Antihypertensive Agents / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D019540:Area Under Curve; D002648:Child; D002675:Child, Preschool; D016001:Confidence Intervals; D004656:Enalapril / Q000097:blood / Q000493:pharmacokinetics* / Q000652:urine; D015773:Enalaprilat / Q000097:blood / Q000652:urine; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood* / Q000652:urine; D007223:Infant; D008297:Male
D000959:Antihypertensive Agents; D004656:Enalapril; D015773:Enalaprilat