The kinetic profiles of enalapril and enalaprilat and their possible developmental changes in pediatric patients with congestive heart failure

Clin Pharmacol Ther. 1994 Aug;56(2):160-8. doi: 10.1038/clpt.1994.119.

Abstract

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)

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Biotransformation
  • Child
  • Child, Preschool
  • Dose-Response Relationship, Drug
  • Enalapril / administration & dosage
  • Enalapril / blood
  • Enalapril / pharmacokinetics*
  • Enalapril / therapeutic use
  • Enalaprilat / blood
  • Enalaprilat / pharmacokinetics*
  • Female
  • Heart Defects, Congenital / complications
  • Heart Failure / drug therapy
  • Heart Failure / metabolism*
  • Humans
  • Infant
  • Infant, Newborn
  • Male

Substances

  • Enalapril
  • Enalaprilat