Pharmacokinetic and clinical evaluation of aztreonam in neonates and premature infants

In order to study serum concentration and urinary concentration (urinary recovery rate) of aztreonam (AZT), AZT was administered via intravenous bolus injection at dose levels of 10 mg/kg, 20 mg/kg and 50 mg/kg to 7 cases of 4 to 26 days old mature or premature infants nearing cure-stage of various bacterial infections upon the treatment with AZT. Clinical evaluation was made in 19 cases with therapy with AZT alone and 13 cases with combination therapy with AZT + ampicillin (ABPC), with a total of 32 cases. The former group included 10 males and 9 females of 0 to 43 days of age and the latter group included 7 males and 6 females of 6 to 41 days of age. All the cases treated with AZT alone including 5 cases for prophylaxis were evaluable. In the 13 combination therapy cases, however, the effect of AZT was evaluable only in 3 cases excluding the cases in which ABPC-susceptible bacteria were the culprits. 1. Changes in serum concentrations and urinary recovery of AZT. Pharmacokinetics of AZT in serum was examined in 5 matured infants at dose levels of 10 mg/kg in 2 cases and 20 mg/kg in 3 cases. Highest levels were observed with the first sampling at 30 minutes after administration in all the cases with values of 29.1 micrograms/ml with 10 mg/kg dose, and 37.8 micrograms/ml and 55.5 micrograms/ml with 20 mg/kg dose in in cases with ages between 4 and 7 days and 1 case with age above 8 days, respectively. Half-life (T 1/2) values were 3.42, 3.05 and 1.58 hours, respectively for the above three groups of patients. As is described here, the T 1/2 value in the infant with age above 8 days was considerably shorter than the T 1/2 values in infants of younger day-ages. Urinary recovery rates of administered AZT were between 10.4 and 52.6%, showing a large individual diversity. In addition to the above cases, one premature infant was administered with AZT (the dose level: 50 mg/kg) and examined for pharmacokinetic parameters at day-ages of 11 days and 19 days. Serum levels of AZT examined were the highest at 30 minutes after dosage (the first sampling) and were 106.8 micrograms/ml at 11 days of age, and 90.4 micrograms/ml at 19 days of age. Serum levels decreased to 16.2 and 9.6 micrograms/ml, respectively, in 8 hours after dosage, at ages of 11 and 19 days. T 1/2 values were 2.62 and 2.35 hours, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)