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[Pharmacokinetic, bacteriological and clinical studies of ceftizoxime in neonates]
1Department of Pediatrics, Meitetsu Hospital.
Insights
Pharmacokinetic studies of ceftizoxime (CZX) in neonates show initial high serum concentrations similar to older children. However, CZX serum half-lives are prolonged in newborns, decreasing with age, and urinary excretion normalizes early.
Area of Science:
- Pharmacology
- Neonatal Medicine
- Antibiotic Pharmacokinetics
Background:
- Ceftizoxime (CZX) is a third-generation cephalosporin antibiotic.
- Understanding the pharmacokinetics of CZX in neonates is crucial for safe and effective therapeutic use.
- Limited data exists on CZX pharmacokinetics specifically in the neonatal population.
Observation:
- Serum concentrations of CZX in neonates (1-27 days) and infants (55-57 days) after a single 20 mg/kg IV dose were measured.
- Serum half-lives and urinary excretion rates of CZX were determined in both neonates and infants.
- Peak serum concentrations at 1/4 hour were comparable between neonates and infants.
Findings:
- Neonatal serum half-lives of CZX were significantly longer (4-5 times) than in older children, decreasing rapidly with postnatal age.
- Urinary excretion rates were initially lower in neonates but normalized to levels seen in infants and older children relatively quickly.
- By approximately two weeks of age, neonatal half-lives approached twice the normal infant values, further shortening with age.
Implications:
- The prolonged half-life in neonates necessitates careful consideration of dosing intervals to avoid toxicity.
- Adjusted dosing regimens may be required for neonates based on postnatal age to achieve therapeutic efficacy.
- These findings contribute to optimizing antibiotic therapy for infections in the neonatal intensive care unit.
Abstract:
Pharmacokinetic, bacteriological and clinical studies of ceftizoxime (CZX) were performed in neonates. 1. Serum concentrations and urinary excretion of CZX were investigated in 12 neonates ranging ages from 1 to 27 days (gestational age, 35-41 weeks; birth weight, 2,150-4,030 g) and 2 infants ranging ages from 55 to 57 days (gestational age, 39-40 weeks; birth weight, 2,320-2,650 g). Each of the subjects was given a single intravenous dose of 20 mg/kg by one shot. Serum concentrations of CZX in the neonates were 24.9-53.7 micrograms/ml at 1/4 hour after intravenous injection, with an average of 40.6 +/- 7.6 micrograms/ml. Serum half-lives of CZX were 1.32-4.75 hours and averaged 2.60 +/- 1.06 hours. Serum concentrations ranged from 2.01 to 14.6 micrograms/ml at 6 hours after injection with an average of 7.70 +/- 3.89 micrograms/ml. In the 2 infants, serum concentrations were 42.0 and 46.2 micrograms/ml at 1/4 hour (average: 44.1 +/- 3.0 micrograms/ml), and 2.91 and 5.04 micrograms/ml at 6 hours after injection (average: 3.98 +/- 1.51 micrograms/ml). Half-lives were 1.54 hours in 1 infant and 1.93 hours in the other (average: 1.74 +/- 0.28 hours). Furthermore, 6-hour urinary recovery rates were 28.5-71.7% (average: 49.3 +/- 12.8%) in the neonates and 42.1-55.5% (average: 48.8 +/- 9.5%) in the infants. The above results suggest that the following 3 points are accepted; 1) peak serum concentrations (at 1/4 hour) in neonates were similar to those in infants and older children irrespective of age (days after birth). 2) Serum half-lives of CZX in neonates shortly after birth were 4 or 5 times longer than those in older children, but decreased rapidly with the advance of day-ages. The half-life in neonates of 2 weeks of age or so became shorter to about twice the normal value in infants. Furthermore, half-lives of the drug in those at an age of the first half of infancy were similar to those in older children. 3) The urinary excretion rates tended to be somewhat low with neonates soon after birth, but became very similar to those in infants and older children at a relatively early stage.(ABSTRACT TRUNCATED AT 400 WORDS)