Abstract
Amrinone (AMR) is an orally effective, positive inotropic agent and vasodilator unrelated pharmacologically to other available drugs, including catecholamines and cardiac glycosides. Clinical studies in adult subjects have demonstrated a close relationship between AMR plasma concentrations and improvement in cardiac index. The disposition of AMR was studied in 6 children (3 neonates and 3 infants <12 mo) receiving the drug for pulmonary hypertension which was unresponsive to other vasodilators.
Subjects received doses of 1-3 mg/kg AMR iv and elimination kinetics were determined following the last dose. In this population the volume of distribution (1.54±.85 L/kg) and drug clearance rate (.29±.21 L/kg/h) of AMR showed marked inter-individual variability. This was attributable to increases in volume of distribution (r=.78, p<.1) and drug clearance rate (r=.91, p<.02) with age. Elimination half-life was similar in neonates (4.9±3.0 h) and infants (3.7±.8h). Hemodynamic and oxymetric data suggested that AMR produced selective although transient pulmonary vasodilitation in the infants but not in the neonates in this study. This difference in response occurred despite a trend to higher AMR peak serum concentrations in the neonatal group than in older infants (6.4±4.1 μg/ml vs. 3.5±1.8 μg/ml).
Important changes in pharmacokinetic and pharmacodynamic properties of AMR occur during the first year of life and will warrant therapeutic drug monitoring of AMR and similar compounds.
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Green, T., Kulik, T., Marchessault, R. et al. DEVELOPMENTAL STUDY OF AMRINONE DISPOSITION IN INFANTS. Pediatr Res 18 (Suppl 4), 153 (1984). https://doi.org/10.1203/00006450-198404001-00361
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DOI: https://doi.org/10.1203/00006450-198404001-00361