AIMS: The aim of this pharmacokinetic study was to describe and quantify population pharmacokinetics of three antibiotics, cefazolin, ampicillin, and ciprofloxacin, used as antibacterial prophylaxis during cardiovascular surgery with the use of extracorporeal circulation (ECC). METHODS: Adult patients undergoing cardiac surgery with ECC were enrolled to this prospective, pharmacokinetic study. An intravenous bolus of 2 g of ampicillin, 2 g of cefazolin or 400 mg of ciprofloxacin was administered 60-30 min before surgery. Blood samples were collected at 15, 30, 45, 60, 120 and 180 min after the administration and at the end of the surgery. Plasma concentrations of the antibiotics were measured using HPLC methods. Serum concentration-time profiles were analyzed using nonlinear mixed-effects modeling approach. RESULTS: A total of 54 patients were enrolled into the study, 20 with ampicillin, 25 cefazolin and 9 ciprofloxacin. For all antibiotics, population pharmacokinetic models have been successfully developed. CONCLUSION: We identified estimated glomerular filtration rate (eGFR) as the main factor determining the achievement of the pharmacokinetic/pharmacodynamic (PK/PD) target in ampicillin or cefazolin and body weight in ciprofloxacin prophylaxis during cardiac surgery with ECC support.

Department of Cardiac Surgery Faculty of Medicine and Dentistry Palacky University Olomouc and University Hospital Olomouc Czech Republic

Department of Pharmacology 1st Faculty of Medicine Charles University Prague and General University Hospital Prague Czech Republic

Department of Pharmacology Faculty of Medicine and Dentistry Palacky University Olomouc and University Hospital Olomouc Czech Republic

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Morisaki A, Hosono M, Sasaki Y, Hirai H, Sakaguchi M, Nakahira A, Seo H, Suehiro S, Shibata T. Evaluation of risk factors for hospital mortality and current treatment for poststernotomy mediastinitis. Gen Thorac Cardiovasc Surg 2011;59(4):261-7. PubMed DOI

Engelman R, Shahian D, Shemin R, Guy TS, Bratzler D, Edwards F, Jacobs M, Fernando H, Bridges C; Workforce on Evidence-Based Medicine, Society of Thoracic Surgeons. The Society of Thoracic Surgeons practice guideline series: Antibiotic prophylaxis in cardiac surgery, part II: Antibiotic choice. Ann Thorac Surg 2007;83(4):1569-76. PubMed DOI

Holley FO, Ponganis KV, Stanski DR. Effect of cardiopulmonary bypass on the pharmacokinetics of drugs. Clin Pharmacokinet 1982;7(3):234-51. PubMed DOI

Hutschala D, Skhirtladze K, Kinstner C, Zeitlinger M, Wisser W, Jaeger W, Hoeferl M, Müller M, Tschernko E. Effect of cardiopulmonary bypass on regional antibiotic penetration into lung tissue. Antimicrob Agents Chemother 2013;57(7):2996-3002. PubMed DOI

Anastasiadis K, Antonitsis P, Argiriadou H, Deliopoulos A, Grosomanidis V, Tossios P. Modular minimally invasive extracorporeal circulation systems; can they become the standard practice for performing cardiac surgery? Perfusion 2015;30(3):195-200. PubMed DOI

Yokoyama Y, Matsumoto K, Yamamoto H, Iguro Y, Imoto Y, Ikawa K, Morikawa N, Ishida S, Okano Y, Watanabe E, Shimodozono Y, Yamada K, Takeda Y. Pharmacokinetics of ampicillin-sulbactam and the renal function-based optimization of dosing regimens for prophylaxis in patients undergoing cardiovascular surgery. J Infect Chemother 2012;18(6):878-82. PubMed DOI

Lanckohr C, Horn D, Voeller S, Hempel G, Fobker M, Welp H, Koeck R, Ellger B. Pharmacokinetic characteristics and microbiologic appropriateness of cefazolin for perioperative antibiotic prophylaxis in elective cardiac surgery. J Thorac Cardiovasc Surg 2016;152(2):603-10. PubMed DOI

Singh S, Nautiyal A. Aortic Dissection and Aortic Aneurysms Associated with Fluoroquinolones: A Systematic Review and Meta-Analysis. Am J Med 2017;130(12):1449-457 PubMed DOI

Kubickova V, Racova Z, Strojil J, Santavy P and Urbanek K. Separation of ampicillin on polar-endcapped phase: Development of the HPLC method to achieve its correct dosage in cardiac surgery. Acta Chromatographica 2021, online first, doi: 10.1556/1326.2021.00957 DOI

Kubíčková V, Šantavý P, Urbánek K. Stanovení plazmatických koncentrací ampicilinu při jednorázovém podání v kardiochirurgické profylaxi. Klin Farmakol Farm 2022;36(1):4-7. (In Czech) DOI

De Cock RF, Piana C, Krekels EH, Danhof M, Allegaert K, Knibbe CA. The Role of Population PK-PD Modelling in Paediatric Clinical Research. Eur J Clin Pharmacol 2011;67 (Suppl 1):5-16. PubMed DOI

Population Pharmacokinetics of Prophylactic Cefazolin in Cardiac Surgery with Standard and Minimally Invasive Extracorporeal Circulation