Pharmacokinetics of cefuroxime in infants and neonates undergoing cardiac surgery.

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Very little data exist regarding the effect of cardiopulmonary bypass (CPB) on cefuroxime (CXM) pharmacokinetics in children less than one year of age. 50mgkg-1 CXM i.v. after induction were followed by 75mgkg-1 into the CPB circuit. In 42 patients undergoing cardiac surgery, 15-20 samples were obtained between 5 and 360min after the first dose. Total CXM concentrations were measured by high-performance liquid chromatography and a pharmacokinetic/pharmacodynamic (PK/PD) modelling was performed. Using a fixed protein binding of 15.6% for CXM, peak plasma concentrations of unbound CXM were 229 ± 52μgml-1 after the first bolus and 341 ± 86μgml-1 on CPB. Nadir concentrations before CPB were 69 ± 20μgml-1 and six hours later decreased to 41 ± 19μgml-1 with and 24 ± 14μgml-1 without CPB. A two-compartment model was fitted with the main covariates body weight, CPB and postmenstrual age (PMA). PK parameters were as follows: systemic clearance, 5.15 [95% CI 4.5-5.8]lh-1 ; central volume of distribution, 11.25 [9.41-13.09]l; intercompartmental clearance, 18.19 [14.79-21.58]lh-1 ; and peripheral volume, 17.07 [15.7-18.5] L. ƒT>MIC of 32μgml-1 for an 8-h time period was between 70 and 100% (2.5-10kg BW). According to our simulation, 25mgml-1 CXM as a primary bolus and into the prime plus a 5mgkg-1 h-1 infusion maintain CXM concentrations continuously above 32μgml-1 . The routine dosing regimen provided was sufficient for prophylaxis, but continuous dosing can provide a higher percentage of ƒT>MIC.