Ralph Gertler1, Michael Gruber2, Gunther Wiesner3, Stanislas Grassin-Delyle4,5, Saïk Urien6, Peter Tassani-Prell3, Klaus Martin3. 1. Klinik für Anaesthesie, operative und allgemeine Intensivmedizin, Notfallmedizin, Klinikum Links der Weser, University Medical Center Hamburg-Eppendorf, Bremen, Germany. 2. Department of Anesthesia, University Hospital Regensburg, Germany. 3. Institute of Anaesthesiology, German Heart Centre Munich, Technical University Munich, Germany. 4. Département des Maladies des Voies Respiratoires, Hôpital Foch, Université Versailles Saint Quentin en Yvelines, Université Paris Saclay, F-92150, Suresnes, France. 5. Plateforme de spectrométrie de masse et INSERM UMR1173, UFR Sciences de la Santé Simone Veil, Université Versailles Saint Quentin en Yvelines, Université Paris Saclay, F-78180, Montigny-le-Bretonneux, France. 6. CIC1419 Inserm Necker-Cochin, URC Paris Descartes Necker Cochin, AP-HP, Paris, France; EAU7323, Université Paris Descartes, Sorbonne Paris Cité, France.
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.
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.
Authors: Dale W Bratzler; E Patchen Dellinger; Keith M Olsen; Trish M Perl; Paul G Auwaerter; Maureen K Bolon; Douglas N Fish; Lena M Napolitano; Robert G Sawyer; Douglas Slain; James P Steinberg; Robert A Weinstein Journal: Am J Health Syst Pharm Date: 2013-02-01 Impact factor: 2.637
Authors: Paul G Ambrose; Sujata M Bhavnani; Christopher M Rubino; Arnold Louie; Tawanda Gumbo; Alan Forrest; George L Drusano Journal: Clin Infect Dis Date: 2006-11-27 Impact factor: 9.079
Authors: John M Costello; Dionne A Graham; Debra Forbes Morrow; Jacqueline Morrow; Gail Potter-Bynoe; Thomas J Sandora; Frank A Pigula; Peter C Laussen Journal: Ann Thorac Surg Date: 2010-06 Impact factor: 4.330
Authors: Annewil van Saet; Saskia N de Wildt; Catherijne A J Knibbe; A D J J C Bogers; Robert J Stolker; Dick Tibboel Journal: Curr Clin Pharmacol Date: 2013-11
Authors: Simon D Harding; Joanna L Sharman; Elena Faccenda; Chris Southan; Adam J Pawson; Sam Ireland; Alasdair J G Gray; Liam Bruce; Stephen P H Alexander; Stephen Anderton; Clare Bryant; Anthony P Davenport; Christian Doerig; Doriano Fabbro; Francesca Levi-Schaffer; Michael Spedding; Jamie A Davies Journal: Nucleic Acids Res Date: 2018-01-04 Impact factor: 16.971
Authors: Ralph Gertler; Michael Gruber; Gunther Wiesner; Stanislas Grassin-Delyle; Saïk Urien; Peter Tassani-Prell; Klaus Martin Journal: Br J Clin Pharmacol Date: 2018-06-15 Impact factor: 4.335
Authors: J Lanoiselée; P J Zufferey; S Hodin; N Tamisier; L Gergelé; J C Palao; S Campisi; S Molliex; J Morel; X Delavenne; E Ollier Journal: Antimicrob Agents Chemother Date: 2020-11-17 Impact factor: 5.191