Pharmacokinetics of cefepime after single and multiple intravenous administrations in healthy subjects

Abstract

The pharmacokinetics of cefepime in 31 young, healthy volunteers were assessed after the administration of single and multiple 250-, 500-, 1,000-, or 2,000-mg intravenous doses. Each subject received a single dose of cefepime via a 30-min intravenous infusion on day 1 of the study. Starting from day 2, subjects received multiple doses of cefepime every 8 h for 9 days, and on the morning of day 11, they received the last dose. Serial blood and urine samples were collected after administration of the first dose and on days 1, 6, and 11. Cefepime concentrations in plasma and urine were assayed by using reverse-phase high-performance liquid chromatography with UV detection. Data were evaluated by noncompartmental methods to determine pharmacokinetic parameters. The mean half-life of cefepime was approximately 2 h and did not vary with the dose or duration of dosing. The regression analyses of peak levels (Cm.) in plasma at the end of the 30-min intravenous infusion and the area under the plasma concentration-versus-time curve (AUC>o.) showed a dose-proportional response. The steady-state volume of distribution (V,,) was approximately 18 liters and was independent of the administered dose. The multiple-dose pharmacokinetic data are suggestive of a lack of accumulation or change in clearance of cefepime on repeated dosing. Cefepime was excreted primarily unchanged in urine. The recovery of intact cefepime in urine was invariant with respect to the dose and accounted for over 80%o of the dose. The values for renal clearance ranged from 99 to 132 ml/min and were suggestive of glomerular filtration as the primary excretion mechanism. It is concluded that cefepime exhibits linear phannacokinetics in healthy subjects.

Lack of pharmacokinetic interaction between cefepime and amikacin in humans

“…In the current study, concurrent administration of cefepime and amikacin did not alter the pharmacokinetics of either antibiotic. The pharmacokinetic properties of cefepime before, during, and after amikacin coadministration and those of amikacin before, during, and after cefepime coadministration were in excellent agreement with the previously reported pharmacokinetic properties of these drugs (4,5,9,17,21).…”

“…In addition, cefepime appears to have a low affinity for chromosomally derived P-lactamases (23). Clinical experience indicates that cefepime is safe and well tolerated when single or multiple (every 8 or 12 h) doses of 250 to 2,000 mg are given by the intravenous (4,5) or intramuscular (9) routes of administration. The pharmacokinetics of this cephalosporin are linear (4,5,9).…”

“…Clinical experience indicates that cefepime is safe and well tolerated when single or multiple (every 8 or 12 h) doses of 250 to 2,000 mg are given by the intravenous (4,5) or intramuscular (9) routes of administration. The pharmacokinetics of this cephalosporin are linear (4,5,9). Over 80% of the administered dose of cefepime is recovered in urine in an unchanged form (4,5,(7)(8)(9).…”

“…The pharmacokinetics of this cephalosporin are linear (4,5,9). Over 80% of the administered dose of cefepime is recovered in urine in an unchanged form (4,5,(7)(8)(9).…”

Rapid analysis of N-methylpyrrolidine in cefepime with thermal desorption ion mobility spectrometry

“…It has been used widely as a broad spectrum antibiotic and is effective against both Gram-positive and Gram-negative bacteria [2], [3] and has been shown to be particularly effective against Gram-negative species compared to other cephalosporin antibiotics. [4] Cefepime is therefore often employed for the treatment of severe systemic and nosocomial bacterial infections including pneumonia, [5] bone and soft tissue infections [6] and febrile neutrophenia.…”