PHARMACOKINETIC, BACTERIOLOGICAL AND CLINICAL STUDIES ON AZTREONAM IN NEONATES

Pharmacokinetic, bacteriological and clinical studies on aztreonam (AZT) were peformed in neonates. The results obtained are summarized as follows. 1. Plasma levels and urinary excretion of AZT were determined in 18 neonates with ages between 1 and 30 days (gestation periods were 36 to 40 weeks and birth weights were 1,890 to 4,300g) and in 2 infants with 54 and 60 days of age (gestation periods were 36 and 40 weeks, and birth weights were 2,300 and 3,300 g, respectively) upon one-shot intravenous injection of AZT 10 mg/kg (7 cases) or 20 mg/kg (11 cases) to the 18 neonates and 20 mg/kg to the 2 infants. Ampicilin (ABPC) 25 mg/kg was simultaneously injected to 5 cases of the neonates given AZT 20 mg/kg by one-shot intravenous injection and plasma concentrations of ABPC in these 5 cases were also studied. Plasma concentrations in neonates at 0.5 hour after intravenous injection of AZT 10 mg/kg were 11.5 to 27.6 μg/ml (average 20.3± 5.5 μg/ml) and decreased with half-lives of 2.72 to 5.70 hours (average 3.81±1.28 hours), and the plasma levels at 8 hours after administration were 3.3 to 8.7 μg/ml (average 5.8± 2.5 μg/ml). In the cases given AZT at 20 mg/kg, plasma levels at 0.5 hour were 12.4 to 48.8 μg/ml (average 35.9± 11.6 μg/ml) and decreased with half-lives of 1.69 to 4.14 hours (average 2.94±0.76 hours) and AZT levels at 8 hours were 1.1 to 10.6 μg/ml (average 5.6±3.6 μg/ml). Urinary recovery rates in the first 8 hours after intravenous injection of the 10 mg/kg group were 15.5 to 61.9% (average 37.8±21.8%) and 16.3 to 62.2% (average 43.5±16.2%) for the 20 mg/kg group. Plasma concentrations in infants after administration of AZT 20 mg/kg were 33.0 to 35.6 μ g/ml (average 34.3± 1.8 μg/ml) at 0.5 hour and decreased with half-lives of 1.76 to 3.77 hours (average 2.77± 1.42 hours) and AZT plasma levels at 8 hours were 1.4 to 5.8 pg/ml (average 3.6±3.1 μg/ml). Urinary recovery rates were 35.4 to 64.8% (average 50.1±20.8%). These results suggested that AZT shows a dose-dependent, high plasma concentration even in the neonatal period, as well as good urinary excretion from an early stage of the administration. Although there were considerable individual differences, the peak values (at 0.5 hour) tended to be lower with the increase of day-age, but showing a tendency with somewhat higher peak levels in premature infants. The half-lives tended to be shorter with the increase of dayage, and they are particularly short in matured infants. Also, plasma concentratio