The pharmacokinetics of cefpirome--rationale for a twelve-hour dosing regimen

Cefpirome is a new broad-spectrum beta-lactam antibiotic that exhibits minimal concentration dependent killing and produces prolonged postantibiotic effects only with Staphylococcus aureus. These pharmacodynamic characteristics suggest that the goal of optimal dosing regimens for cefpirome is to provide serum levels above the MIC of infecting pathogens for most of the dosing interval. Cefpirome has a half-life of 2.0 hours in normal volunteers that increases to 3.1 to 4.4 hours in elderly patients. Serum concentrations following 0.5, 1.0 and 2.0 grams of cefpirome are above the MIC of common pathogens for more than half of the dosing interval. For many of the Enterobacteriaceae, serum concentrations are above the MIC for over 12 hours. The drug distributes primarily into extracellular fluid and does provide potentially therapeutic concentrations in cerebrospinal fluid (CSF). The drug is eliminated primarily by the kidney and requires dosage modification when the creatinine clearance is below 50 ml/min. The half-life of the drug is not significantly altered in patients with cystic fibrosis and hepatic dysfunction. The integration of the drug's pharmacokinetic and pharmacodynamic characteristics support the use of a 12-hour dosing interval for the treatment of serious infection.