Gertler, Ralph and Gruber, Michael and Wiesner, Gunther and Grassin-Delyle, Stanislas and Urien, Saik and Tassani-Prell, Peter and Martin, Klaus (2018) Pharmacokinetics of cefuroxime in infants and neonates undergoing cardiac surgery. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY, 84 (9). pp. 2020-2028. ISSN 0306-5251, 1365-2125
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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 75mg 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 mu g ml(-1) after the first bolus and 341 +/- 86 mu gml(-1) on CPB. Nadir concentrations before CPB were 69 +/- 20 mu gml(-1) and six hours later decreased to 41 +/- 19 mu g ml-1 with and 24 +/- 14 mu g 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. fT > MIC of 32 mu g 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 mu g ml(-1). CONCLUSIONS The routine dosing regimen provided was sufficient for prophylaxis, but continuous dosing can provide a higher percentage of fT > MIC.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SURGICAL SITE INFECTIONS; CRITICALLY-ILL PATIENTS; CARDIOPULMONARY BYPASS; ANTIBIOTIC-PROPHYLAXIS; PLASMA-CONCENTRATIONS; PROTEIN-BINDING; POPULATION PHARMACOKINETICS; PHARMACODYNAMIC PARAMETERS; CARDIOVASCULAR-SURGERY; CEFAZOLIN; antibiotic prophylaxis; cardiac surgical procedures; cefuroxime; heart defects; congenital; pharmacokinetics |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Anästhesiologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Jan 2020 15:17 |
| Last Modified: | 09 Jan 2020 15:17 |
| URI: | https://pred.uni-regensburg.de/id/eprint/14000 |
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