Pharmacokinetics of cefuroxime in infants and neonates undergoing cardiac surgery

Aims: Very little data exist regarding the effect of cardiopulmonary bypass (CPB) on cefuroxime (CXM) pharmacokinetics in children less than one year of age. Methods: 50 mg kg⁻¹ CXM i.v. after induction were followed by 75 mg kg⁻¹ into the CPB circuit. In 42 patients undergoing cardiac surgery, 15–20 samples were obtained between 5 and 360 min after the first dose. Total CXM concentrations were measured by high-performance liquid chromatography and a pharmacokinetic/pharmacodynamic (PK/PD) modelling was performed. Results: Using a fixed protein binding of 15.6% for CXM, peak plasma concentrations of unbound CXM were 229 ± 52 μg ml⁻¹ after the first bolus and 341 ± 86 μg ml⁻¹ on CPB. Nadir concentrations before CPB were 69 ± 20 μg ml⁻¹ and six hours later decreased to 41 ± 19 μg ml⁻¹ with and 24 ± 14 μg ml⁻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] l h⁻¹; central volume of distribution, 11.25 [9.41–13.09] l; intercompartmental clearance, 18.19 [14.79–21.58] l h⁻¹; and peripheral volume, 17.07 [15.7–18.5] L. ƒT > MIC of 32 μg ml⁻¹ for an 8-h time period was between 70 and 100% (2.5–10 kg BW). According to our simulation, 25 mg ml⁻¹ CXM as a primary bolus and into the prime plus a 5 mg kg⁻¹ h⁻¹ infusion maintain CXM concentrations continuously above 32 μg ml⁻¹. Conclusions: The routine dosing regimen provided was sufficient for prophylaxis, but continuous dosing can provide a higher percentage of ƒT > MIC.