CEFEPIME CLINICAL PHARMACOKINETICS

Cefepime is a new parenteral cephalosporin with antimicrobial activity similar to third-generation cephalosporins. It acts against the Enter obacteriaceae family, and Pseudomonas aeruginosa, but maintains Gram-p ositive activity similar to that of first- or second-generation cephal osporins. Cefepime has in vitro activity against many bacterial isolat es resistant to ceftazidime and cefotaxime, is stable against chromoso mally 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-abdo minal and urinary tract infections, skin and soft tissue infections an d for prophylaxis in biliary tract and prostate surgery. Pharmacokinet ic studies indicate that cefepime exhibits linear pharmacokinetic beha viour. Pharmacokinetic variables am not significantly different betwee n single- and multiple-dose administration, indicating a lack of drug accumulation in patients with normal renal function. Cefepime is not h ighly bound to plasma proteins, with binding values of approximately 1 6 to 19%. The drug is widely distributed in various biological tissues and fluids. The primary route of elimination is from the kidneys, wit h over 80% of the drug recovered in the urine as unchanged drug in pat ients with normal renal function. Total drug clearance and renal clear ance are similar to creatinine clearance, and glomerular filtration is thought to be the primary mechanism of renal excretion. The eliminati on half-life is approximately 2 to 2.5h in patients. Cefepime is remov ed by haemodialysis (over 3h) and peritoneal dialysis (over 72h) to an appreciable extent, with 40 to 68% and 26% of the drug removed, respe ctively. Overall, cefepime is well tolerated by patients and no signif icant drug interactions have been reported to date.