The pharmacokinetic profile of a new generation of parenteral cephalosporin

Cefepime, a fourth-generation cephalosporin with activity against both gram-negative and gram-positive organisms, has been investigated in healthy subjects and in special patient populations, including the elderly and those whose ability to eliminate drugs may be compromised. This review of seven pharmacokinetic studies indicates that the pharmacokinetic disposition of cefepime, administered either intravenously or intramuscularly, is similar to that of other cephalosporins with regard to dose linearity, renal excretion, and low serum protein binding. The elimination half-life of intravenous cefepime has been found to be approximately 2 hours, and peak serum concentrations approach 82 g/mL for a 1-g dose and 164 μg/ML for a 2-g dose. Total body clearance is approximately 120 mL/min, independent of dose, and >80% of the drug is excreted unchanged by the kidneys. Dosage adjustment is warranted for patients with renal insufficiency but not hepatic dysfunction. The pharmacokinetic disposition of cefepime is altered in the elderly but not enough to necessitate additional dosage adjustment. Tissue penetration studies indicate similarity to other cephalosporins with low protein binding.