Premium
Pharmacokinetics of cefuroxime in infants and neonates undergoing cardiac surgery
Author(s) -
Gertler Ralph,
Gruber Michael,
Wiesner Gunther,
GrassinDelyle Stanislas,
Urien Saïk,
TassaniPrell Peter,
Martin Klaus
Publication year - 2018
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.13632
Subject(s) - pharmacokinetics , volume of distribution , medicine , cefuroxime , bolus (digestion) , cardiac surgery , intravenous bolus , anesthesia , cardiopulmonary bypass , body surface area , cardiac index , pharmacodynamics , urology , cardiac output , hemodynamics , surgery , pharmacology , antibiotics , chemistry , biochemistry
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. ƒ 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 ƒ T > MIC.