Cefepime Clinical Pharmacokinetics

Abstract

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.

Rapid high-performance liquid chromatographic determination of cefepime in human plasma

“…Cefepime is active in vitro against bacterial pathogens causing biliary tract infections, including Pseudomonas spp., Escherichia coli, Klebsiella spp., Citrobacter spp., Proteus mirabilis and other enterobacteriaceae, in addition to Gram-positive and some Gram-negative anaerobes (Kieft et al, 1993). Clinical uses 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 (Okamoto et al, 1993).…”

“…The elimination half-life (T 1/2 ) is approximately 2 h and is dose-independent (Barbhaiya et al, 1992;Kalman et al, 1992;Okamoto et al, 1993;Barradell and Bryson 1994;Van der Auwera and Santelia 1993;Rybak, 1996). The elimination half-life increases in patients with renal impairment.…”

“…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 (Barbhaiya et al, 1992;Okamoto et al, 1993;Van der Auwera and Santella, 1993;Barradell and Bryson, 1994;Rybak, 1996). Total clearance (Cl tot ) varies between 120 and 152 mL/min (Barbhaiya et al, 1992;Van der Auwera et al, 1993;Rybak, 1996).…”

The effect of different doses of cisplatin on the pharmacokinetic parameters of cefepime in mice

“…Cefepime was our test drug, and its clearance was regarded as appropriately similar to creatinine clearance (Okamoto et al 1993). On using 18 or 22 mg/ kg of cisplatin, the lethality did not differ significantly from the control group, while the elimination half-life of cefepime was significantly prolonged.…”

“…The renal clearance of cefepime approximates to creatinine clearance, and renal impairment does not affect cefepime non-renal clearance and volume of distribution (Okamoto et al 1993).…”