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. Design: Prospective study. Setting:Pediatric intensive care unit in a university hospital. Participants: Fifteen neonates aged less than 1 month with transposition of the great arteries and 14 infants aged 2 to 6 months with complete atriove ntricular septal defect. Interventions: Amrinone, loading dose of 2 mg/kg, was administered before weaning from cardiopulmonary bypass, followed by a maintenance infusion of 7.5 mu g/kg/min. Measurements and Main Results: Blood samples to determine plasma concentrat ions of amrinone, N-acetylamrinone, and N-glycolylamrinone were drawn befor e amrinone administration, frequently after the loading dose, every 6 hours during the maintenance infusion, and until 48 hours after the end of the i nfusion. 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 stead y-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 h ours in infants (p < 0.05). There was a linear correlation between the clea rance 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 no t differ between neonates and infants. Conclusions Amrinone is eliminated at a slower rate in neonates than in inf ants. The rate of acetylation of amrinone appears to be similar; the differ ences in the elimination capacity of amrinone are mainly due to the immatur e renal function in neonates, Copyright (C) 2000 by W.B. Saunders Company.