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. 1985 Dec;28(6):791–795. doi: 10.1128/aac.28.6.791

Cefotaxime and desacetylcefotaxime pharmacokinetics in infants and children with meningitis.

J M Trang, R F Jacobs, G L Kearns, A L Brown, T G Wells, F L Underwood, R B Kluza
PMCID: PMC180330  PMID: 4083862

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.

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Selected References

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