Pharmacokinetics of cefuroxime in infants and neonates undergoing cardiac surgery

摘要

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. ? T??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 ? T??MIC.