Pharmacokinetics of cefotaxime in neonates

Abstract

The effects of gestational age on the pharmacokinetics of cefotaxime and its desacetyl metabolite during the first days of life was investigated in a group of four full-term infants and 12 preterm infants of less than 35 weeks gestation. Half of the preterm infants had received betamethasone, a drug known to facilitate hepatic microsomal drug metabolism, whilst the others had not. No significant differences in the pharmacokinetics of cefotaxime were observed between the various groups, with elimination half-life (T 1/2 beta) of cefotaxime ranging from 4.04 +/- 1.52 to 4.56 +/- 1.31 h. The desacetyl metabolite of cefotaxime was present in all post-dose serum samples, irrespective of the gestational age of the baby. Its formation was apparently unaffected by prior exposure to betamethasone. The elimination half-life of cefotaxime is significantly longer in newborn infants than in older children or adults, this increase probably results from decreased renal excretion of the drug, rather than from immaturity in its metabolism. A dose of 50 mg/kg of cefotaxime given every 12 h is appropriate for infants of less than seven days old.

Serum Concentrations of Cefotaxime and its Metabolite Desacetyl-cefotaxime in Infants and Children During Continuous Infusion

“…This indicates that the enzyme systems for cefotaxime metabolism are available as early as 32 weeks of gestational age as consistent with previous data [10].…”

“…Among the factors to be considered in the explanation of this wide range of distribution are differences in renal clearance (such as differences in GFR and in renal tubular excretion) and differences in liver metabolism. These factors have been a subject of investigation in smaller series of children receiving intermittent cefotaxime administration [10,20], and have been reported to change during the first days after birth [21,22]. The present study underscores the wide variability in serum concentrations.…”

“…Despite its widespread use, surprisingly few data exist on the pharmacokinetics of cefotaxime and its metabolite during continuous infusion, in particular in infants and children. Studies performed until present described pharmacokinetics during intermittent dosage regimes in this age group [6][7][8][9][10]. These studies show that the elimination half-life of cefotaxime is prolonged in neonates, due to decreased renal excretion.…”

Cefotaxime and desacetylcefotaxime pharmacokinetics in infants and children with meningitis

“…The mean CL of Ctx in our subjects (0.289 liter/h per kg) was in close agreement with values reported for adults with normal renal function (approximately 0.234 to 0.307 liter/h per kg) after Ctx quantitation by HPLC (16,29). The differences between CL of Ctx in our patients and that in full-term, newborn infants (2,26) were consistent with expected developmental differences in renal function and body mass-water relationships between the two age groups.…”

A Population and Developmental Pharmacokinetic Analysis To Evaluate and Optimize Cefotaxime Dosing Regimen in Neonates and Young Infants

“…All these observations of routine care highlight the urgent requirement for powerful pharmacokinetic data for this vulnerable population. Previous studies assessing the pharmacokinetics of cefotaxime in neonates included a relatively small number of patients (n Յ 37) (18,(22)(23)(24)(25)(26)(27)(28)(29) and did not precisely quantify the impact of maturation on the disposition of cefotaxime. Previous mean estimates of cefotaxime clearance in term neonates varied from 0.09 liter/ h/kg to 0.14 liter/h/kg (5).…”