Pharmacokinetic Study of Cefazolin in Short Daily Hemodialysis

A number of centers across the world offer short daily hemodialysis (SDHD) treatments. To date, cefazolin pharmacokinetics have not been described in patients undergoing SDHD.

The purpose of this study was to investigate the effect of SDHD on the pharmacokinetics of cefazolin.

This was a prospective, open-label, pharmacokinetic study of cefazolin during SDHD in 10 noninfected patients. Participants received a 1-g intravenous (IV) infusion of cefazolin after SDHD on study day 1 and a second dose after SDHD on study day 2. To determine the concentration of cefazolin, 6 blood samples were drawn at 0, 1, 2, 2.3, 4, and 24 hours after initiation of dialysis on day 2, and 2 dialysate samples were drawn at 1 and 2 hours after initiation of dialysis on day 2. Samples were analyzed using high-performance liquid chromatography, and pharmacokinetic parameters were determined.

Median interdialysis clearance was 0.16 L/h (interquartile range [IQR]: 0.11-0.21 L/h), and median intradialysis clearance was 1.95 L/h (IQR: 1.66-2.45 L/h). Median interdialysis half-life was 28.2 hours (IQR: 23.5-59.3 hours) as compared with a median intradialysis half-life of 2.3 hours (IQR: 1.7-2.7 hours). The median percentage removal of cefazolin during dialysis was 41% (IQR: 35%-53%). Conclusion and Relevance: Estimated cefazolin dialysis clearance is similar to previous estimates with conventional thrice-weekly regimens. Current dosing recommendations of 1 g IV post-SDHD achieve total serum drug concentrations greater than 40 mg/L in all patients, which is the total drug concentration required for bactericidal activity against Staphylococcus species.