ABSTRACT
To define the relationship between digoxin dose and plasma concentration and the changes in body growth, 1181 plasma digoxin levels were measured in 644 infants and children receiving maintenance digoxin therapy. The drug was given intravenously to 166 patients and orally to 478. A significant linear correlation between dose and plasma concentration was observed (r 0.346 to 0.767 in the intravenous and 0.264 to 0.664 in the oral groups). Dosage differences explained 7% to 60% of the variability in digoxin plasma concentrations in various age and weight groups. The linear regression slope was greater in younger age groups, especially preterm infants weighing less than 1500 gm, and tended to decrease with age. The data (1) allow an approximate prediction of plasma concentrations of digoxin and their variability associated with changes in dosages in various pediatric age and weight groups, (2) permit an estimate of other pharmacokinetic determinants of digoxin plasma concentration and their changes with age, and (3) suggest that larger changes in digoxin doses in older children are necessary to achieve the same change in serum concentration that is achieved with smaller dose changes in the young infant. As a result, premature infants are more sensitive to and require smaller digoxin doses.
Subject(s)
Digoxin/metabolism , Age Factors , Body Weight , Child , Child, Preschool , Digoxin/administration & dosage , Digoxin/blood , Drug Administration Schedule , Humans , Infant , Infant, Newborn , Infant, Premature , Kinetics , Radioimmunoassay , Reagent Kits, DiagnosticABSTRACT
Indomethacin is currently used for the pharmacologic closure of PDA in preterm infants with respiratory distress syndrome. However, the response to the drug has been variable and the disposition of the drug in preterm infants is not well understood. We studied the pharmacokinetics of indomethacin in nine preterm infants with birth weights ranging from 800 to 1,960 gm and gestational ages of 28 to 36 weeks. Three different dose schedules (0.1, 0.25, 0.3 mg/kg dose) were used. The plasma half-life of indomethacin ranged from 11 to 20 hours. Peak levels were achieved within four hours and ranged from 0.027 to 0.310 microgram/ml. The half-life in infants less than 32 weeks' gestation was significantly prolonged compared to that in infants greater than 32 weeks. Protein-binding studies with 14C indomethacin showed that 98% of indomethacin was protein bound. Absorption of orally administered indomethacin appears to be poor and incomplete. No immediate major complications could be correlated to indomethacin therapy in this study.