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 CXM i.v. after induction were followed by 75 mg kg 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 after the first bolus and 341 ± 86 μg ml on CPB. Nadir concentrations before CPB were 69 ± 20 μg ml and six hours later decreased to 41 ± 19 μg ml with and 24 ± 14 μg ml 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 ; central volume of distribution, 11.25 [9.41-13.09] l; intercompartmental clearance, 18.19 [14.79-21.58] l h ; and peripheral volume, 17.07 [15.7-18.5] L. ƒT > MIC of 32 μg ml for an 8-h time period was between 70 and 100% (2.5-10 kg BW). According to our simulation, 25 mg ml CXM as a primary bolus and into the prime plus a 5 mg kg  h infusion maintain CXM concentrations continuously above 32 μg ml .

Conclusions: The routine dosing regimen provided was sufficient for prophylaxis, but continuous dosing can provide a higher percentage of ƒT > MIC.