Pharmacokinetics of cefpirome during continuous venovenous hemofiltration:: Rationale for an 8-hour dosing interval

Objective Cefpirome is a new semisynthetic cephalosporin, primarily eliminated by the kidneys, that requires dosage adjustment in patients with kidney failure. The optimal dosing regimen of cefpirome in patients with continuous veno-venous hemofiltration (CVVH) is unknown. Methods: Pharmacokinetic properties of cefpirome were investigated in eight anuric patients with acute kidney failure treated by CVVH, All patients received a dosage of 2 g cefpirome every 8 hours after starting the hemofiltration with high-flux polysulfone membranes. Concentrations of cefpirome in plasma and ultrafiltrate were measured by HPLC. Results: Total clearance and hemofiltration clearance of cefpirome were 589.1 +/- 164.5 mL/min and 43.3 +/- 7.8 mL/min, respectively. serum elimination half-life was 2.36 +/- 0.59 hours, The highest plasma drug concentration was 14.8 +/- 3.2 mu g/mL, and it declined to trough levels of 3.1 +/- 0.8 mu g/mL at the end of the dosing interval. Conclusion: On the basis of previously published pharmacodynamic characteristics of cefpirome and the pharmacokinetic parameters obtained in this study, we calculated a required total daily dose of 2 g every 8 hours to achieve sufficient plasma antibiotic levels to cover the majority of target pathogens. However, this dosage may be insufficient during CVVH for intermediate resistant strains of Pseudomonas aeruginosa.