Cefotaxime and desacetylcefotaxime pharmacokinetics in infants and children with meningitis

Abstract

The pharmacokinetics and cerebrospinal fluid (CSF) penetration of cefotaxime (Ctx) and desacetylcefotaxime (dCtx) were evaluated in 13 infants and children with meningitis after dose 6 of Ctx in a multiple-dose intermittent intravenous infusion regimen (50 mg/kg every 6 h). Model-dependent and noncompartmental pharmacokinetic parameters were determined and were found to be congruous. The disposition of both Ctx and dCtx was described adequately by a one-compartment, open model. Noncompartmental pharmacokinetic parameters are reported. The mean Ctx serum concentration at 0.25 h postinfusion was 121.2 micrograms/ml, and the mean CSF concentration at 1 h postinfusion was 6.2 micrograms/ml. The CSF/serum ratio was variable (0 to 20%), with a mean penetration of 10.1%. The mean Ctx elimination half-life, apparent steady-state volume of distribution, and total body clearance were 0.8 h, 0.361 liter/kg, and 0.289 liter/h per kg, respectively. For Ctx, 61% of the dose was excreted unchanged in the urine during the 6-h postinfusion period, and the estimated renal clearance was 0.174 liter/h per kg. No significant correlations were observed between Ctx pharmacokinetic parameters and demographic parameters. The mean peak concentration of dCtx in serum (21.6 micrograms/ml) occurred at approximately 1.5 h postinfusion, and the mean concentration in CSF at 1 h postinfusion was 5.6 micrograms/ml. The CSF/serum ratio was extremely variable (0 to 103%), and the mean penetration was 28.8%. The mean apparent elimination half-life for dCtx was 2.1 h. In infants and children with normal renal function, a 50-mg/kg dose of Ctx administered every 6 h should provide adequate concentrations in serum and CSF in the majority of patients with meningitis.