Pharmacokinetics of fentanyl in neonates

The pharmacokinetics of fentanyl were studied in fourteen neonates undergoing major surgical procedures. Five patients were less than 1 day of age, seven were 1-4 days old, and two were 7-14 days old. Fentanyl was given intravenously, 10 μg/kg (n = 1), 25 μg/kg (n = 4), or 50 μg/kg (n = 9), and plasma concentrations measured at intervals of up to 18 hr. Average weight was 2.9 kg. The injection of 25 or 50 μg/kg of fentanyl over 1-3 min was hemodynamically well-tolerated by all patients. Four newborns without respiratory impairment secondary to surgery or disease needed ventilatory support for an average of 24 hr (range 11-40 hr). Plasma concentrations of fentanyl were most appropriately described by a two-compartment model. The mean ± SEM values of selected model parameters were volume of the central compartment, 1.45 ± 0.34 L/kg; volume of distribution at steady state, 5.1 ± 1 L/kg; clearance, 17.94 ± 4.38 ml·kg^-1·min^-1; and terminal elimination half-life (t( 1/2 )β), 317 ± 70 min, In seven patients transient rebound in plasma fentanyl concentrations of 0.5 ng/ml or greater occurred. In three patients with markedly increased intraabdominal pressure, the t( 1/2 )β was 1.5-3 times the population mean. Thus fentanyl disposition in neonates is highly variable, but the t( 1/2 )β is predictably prolonged in the presence of increased abdominal pressure.