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[Studies on the pharmacokinetics of cefotaxime in neonates]
Abstract:
The pharmacokinetics of cefotaxime was investigated in neonates. The following results were obtained. 1. The peak serum concentration of cefotaxime, seen 15-minutes after a single intravenous of 20 mg/kg, was 51.6 +/- 9.3 mcg/ml by bioassay. After 6 hours the mean serum concentration decreased to 5.6 +/- 3.1 mcg/ml. Concentrations obtained by HPLC paralleled those determined by bioassay. The peak serum concentration of the desacetyl metabolite was attained 30 minutes to 2 hours after injection. The mean serum desacetyl metabolite concentration was about 1/2.5 times higher than the cefotaxime concentration. The half-life was inversely related to the age of the neonates, decreasing to 1.64 hours on day 11 postpartum. 2. Serum concentrations determined by bioassay and HPLC after administering a dose of 10 mg/kg of cefotaxime by 30-minute intravenous drip infusion were comparable. The peak serum concentration at the completion of intravenous drip infusion was 21.0 mcg/ml by bioassay. The half-life of cefotaxime was 2.85 hours. The peak serum concentration of the desacetyl metabolite, seen at the completion of intravenous drip infusion, was about 1/2 times that of the peak cefotaxime concentration. 3. The peak serum concentration at the completion of a 30-minute intravenous drip infusion of 20 mg/kg displayed a mean value of 33.5 +/- 10.3 mcg/ml by bioassay. After 6 hours the mean serum concentration was 4.0 +/- 1.0 mcg/ml. The peak serum concentration of the desacetyl metabolite, seen at the completion of infusion to 2 hours thereafter, was equivalent to about 1/2.2 the peak cefotaxime concentration. 4. Mean urinary excretion rate of cefotaxime in 2-day-old neonates was 23.4% by bioassay 6 hours after a 30-minute intravenous drip infusion of 10 mg/kg. The mean urinary excretion rate of the desacetyl metabolite was 8.7%. Mean 6-hour excretion rates in 2-day-old and 4-day-old neonates administered 20 mg/kg of cefotaxime by 30-minute intravenous drip infusion were 6.2% and mean 37.7%, respectively. The corresponding values for the desacetyl metabolite were 2.4% and 12.4%, respectively.