Pharmacokinetics of cefuroxime in infants and neonates undergoing cardiac surgery

Abstract

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.

Keywords: antibiotic prophylaxis; cardiac surgical procedures; cefuroxime; heart defects, congenital; pharmacokinetics.

Figure 1

Dosing simulation according to the standard (A), every 4 h (B) or every 2 h boli (C) or a bolus with infusion and a CPB prime bolus (D) in children with a bodyweight between 2.5 and 10 kg. Predictions are based on PK parameters calculated from unbound plasma concentrations. Horizontal lines illustrate 32 mg l⁻¹ values. 5, 50 and 95 percentiles are given