Pharmacokinetics of amrinone in neonates and infants.
OBJECTIVE
To evaluate the pharmacokinetics of amrinone and its metabolites in neonates and infants after reconstructive surgery for congenital heart disease.


METHODS
Prospective study.


METHODS
Pediatric intensive care unit in a university hospital.


METHODS
Fifteen neonates aged less than 1 month with transposition of the great arteries and 14 infants aged 2 to 6 months with complete atrioventricular septal defect.


METHODS
Amrinone, loading dose of 2 mg/kg, was administered before weaning from cardiopulmonary bypass, followed by a maintenance infusion of 7.5 microg/kg/min.


RESULTS
Blood samples to determine plasma concentrations of amrinone, N-acetylamrinone, and N-glycolylamrinone were drawn before amrinone administration, frequently after the loading dose, every 6 hours during the maintenance infusion, and until 48 hours after the end of the infusion. Amrinone clearance was 2.4 +/- 0.9 mL/kg/min in neonates and 3.2 +/- 1.2 mL/kg/min in infants (p < 0.05). The volume of distribution at steady-state was smaller (p < 0.05) in neonates than in infants. The elimination half-life of amrinone was 10.7 +/- 6.7 hours in neonates and 6.1 +/- 1.4 hours in infants (p < 0.05). There was a linear correlation between the clearance of amrinone and the body surface area (r = 0.67; p < 0.05). The ratio of the plasma concentration of N-acetylamrinone to that of amrinone did not differ between neonates and infants.


CONCLUSIONS
Amrinone is eliminated at a slower rate in neonates than in infants. The rate of acetylation of amrinone appears to be similar; the differences in the elimination capacity of amrinone are mainly due to the immature renal function in neonates.
Laitinen
P
P
Department of Anesthesiology, Hospital for Children and Adolescents, Helsinki, Finland.
Ahonen
J
J
Olkkola
K T
KT
Peltola
K
K
Rautiainen
P
P
Räsänen
J
J
D000676:Amrinone / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D002315:Cardiopulmonary Bypass; D002316:Cardiotonic Agents / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006330:Heart Defects, Congenital / Q000601:surgery; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000493:pharmacokinetics*; D011446:Prospective Studies
D002316:Cardiotonic Agents; D010726:Phosphodiesterase Inhibitors; C023499:N-acetylamrinone; D000676:Amrinone