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 microg/mL, and it declined to trough levels of 3.1 +/- 0.8 microg/mL at the end of the dosing interval.


CONCLUSIONS
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.
Banyai
M
M
Department of Cardiology, Institute of Virology, University of Vienna, Austria.
Thalhammer
F
F
El-Menyawi
I
I
Heinz
G
G
Traunmüller
F
F
Siostrzonek
P
P
D058186:Acute Kidney Injury / Q000188:drug therapy* / Q000378:metabolism; D001002:Anuria / Q000188:drug therapy* / Q000378:metabolism; D019540:Area Under Curve; D002511:Cephalosporins / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use; D002851:Chromatography, High Pressure Liquid; D005260:Female; D006207:Half-Life; D006440:Hemofiltration; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D000097572:Cefpirome
D002511:Cephalosporins; D000097572:Cefpirome