Cefepime clinical pharmacokinetics

Cefepime is a new parenteral cephalosporin with antimicrobial activity similar to third-generation cephalosporins. It acts against the Enterobacteriaceae family, and Pseudomonas aeruginosa, but maintains Gram-positive activity similar to that of first- or second-generation cephalosporins. Cefepime has in vitro activity against many bacterial isolates resistant to ceftazidime and cefotaxime, is stable against chromosomally mediated beta-lactamases, demonstrates lower affinity for these enzymes and shows a high resistance to enzymatic hydrolysis. Clinical uses thus far include treatment of lower respiratory tract, intra-abdominal and urinary tract infections, skin and soft tissue infections and for prophylaxis in biliary tract and prostate surgery. Pharmacokinetic studies indicate that cefepime exhibits linear pharmacokinetic behaviour. Pharmacokinetic variables are not significantly different between single- and multiple-dose administration, indicating a lack of drug accumulation in patients with normal renal function. Cefepime is not highly bound to plasma proteins, with binding values of approximately 16 to 19%. The drug is widely distributed in various biological tissues and fluids. The primary route of elimination is from the kidneys, with over 80% of the drug recovered in the urine as unchanged drug in patients with normal renal function. Total drug clearance and renal clearance are similar to creatinine clearance, and glomerular filtration is thought to be the primary mechanism of renal excretion. The elimination half-life is approximately 2 to 2.5 h in patients. Cefepime is removed by haemodialysis (over 3h) and peritoneal dialysis (over 72h) to an appreciable extent, with 40 to 68% and 26% of the drug removed, respectively. Overall, cefepime is well tolerated by patients and no significant drug interactions have been reported to date.