Abstract
The purpose of this investigation was to study the effects of renal function on the pharmacokinetics and pharmacodynamics (PK-PD) of free cefazolin administered prophylactically in cardiothoracic surgery. Patients received an initial 2-g dose of cefazolin, followed by 1-g doses 6, 12, 18 and 24 h after the first dose. In patients who underwent cardiopulmonary bypass, 1 g was added to the priming solution. In 35 patients with a normal estimated creatinine clearance (CLcr) ≥50 ml/min, a free cefazolin concentration <4 μg/ml was observed in 11.4, 5.7 and 54.3% of patients before the second dose, at the end and 24 h after operation, respectively. In contrast, only 7.4% of 27 patients with CLcr <49 ml/min had a free cefazolin concentration <4 μg/ml 24 h after the operation. There was a high negative correlation between CLcr and time above the target minimal inhibitory concentration (MIC) when the CLcr was <50 ml/min (r 2 = 0.807), and no correlation when the CLcr was ≥50 ml/min. Renal function has a significant impact on the PK-PD of prophylactic cefazolin in cardiothoracic surgery. The postoperative drug dosing intervals should be <6 h in order to achieve a 100% time above the MIC in patients with CLcr ≥ 50 ml/min.
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Acknowledgements
We thank Astellas Pharma Inc., Tokyo, Japan, and Shionogi & Co., Ltd., Osaka, Japan, for kindly supplying us with cefazolin and cephalexin, respectively. We also thank the staff of the Department of Pharmacokinetics at Kyoto Pharmaceutical University, School of Pharmacy, for their contributions to this study, and Yukimi Shibata, M.E., from the Kyoto Prefectural University of Medicine, University Hospital, for reviewing the manuscript.
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Kosaka, T., Hosokawa, K., Shime, N. et al. Effects of renal function on the pharmacokinetics and pharmacodynamics of prophylactic cefazolin in cardiothoracic surgery. Eur J Clin Microbiol Infect Dis 31, 193–199 (2012). https://doi.org/10.1007/s10096-011-1293-z
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DOI: https://doi.org/10.1007/s10096-011-1293-z