The kinetic profiles of enalapril and enalaprilat and their possible developmental changes in pediatric patients with congestive heart failure.
Enalapril and enalaprilat concentrations were measured after enalapril maleate (0.05 to 0.3 mg/kg) was administered orally to 12 pediatric patients (age range, 10 days to 6 1/2 years) with congestive heart failure caused by congenital heart disease and compared with those obtained from seven normal adults (age range, 21 to 39 years). When normalized to the oral 1 mg/m2 dose of enalapril maleate, the mean +/- SD area under the serum concentration-time curve (AUC) of enalaprilat, a pharmacologically active angiotensin-converting enzyme inhibitor, did not differ significantly between the pediatric group aged > 20 days and adult group (83.1 +/- 47.0 versus 64.6 +/- 17.8 ng.hr/ml per 1 mg/m2). When normalized to the oral 0.1 mg/kg dose, the mean AUC was significantly (p < 0.05) smaller in this pediatric group than in the adult group (138.4 +/- 69.2 versus 245.7 +/- 61.8 ng.hr/ml per 0.1 mg/kg). The AUC observed in three younger (age < 20 days) subjects tended to be much greater compared with infants aged > 20 days. The mean AUC ratio of enalaprilat to enalapril was significantly (p < 0.05) lower in the older pediatric subgroup (2.0 +/- 1.0) than in the adult group (3.4 +/- 1.6), whereas the mean ratios were comparable between the two subdivided pediatric groups. The results suggest that the oral enalapril dose would be better determined on a body surface area rather than on a body weight basis in pediatric patients with congestive heart failure aged > 20 days. The oral dosage should be much reduced in infants with congestive heart failure aged < 20 days compared with those aged > 20 days.(ABSTRACT TRUNCATED AT 250 WORDS)
Nakamura
H
H
Division of Clinical Pharmacology, National Medical Center, Tokyo, Japan.
Ishii
M
M
Sugimura
T
T
Chiba
K
K
Kato
H
H
Ishizaki
T
T
D000284:Administration, Oral; D000328:Adult; D001711:Biotransformation; D002648:Child; D002675:Child, Preschool; D004305:Dose-Response Relationship, Drug; D004656:Enalapril / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D015773:Enalaprilat / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D006330:Heart Defects, Congenital / Q000150:complications; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male
D004656:Enalapril; D015773:Enalaprilat