Lack of pharmacokinetic interaction between cefepime and amikacin in humans

Abstract

The interaction potential between cefepime and amikacin was investigated in a steady-state pharmacokinetic study in 16 healthy male subjects. Eight subjects (group A) received a first course of 2,000 mg of cefepime; this was followed by a second course of 2,000 mg of cefepime with 300 mg of amikacin and a third course of 2,000 mg of cefepime. Eight other subjects (group B) received a first course of 300 mg of amikacin, a second course of 300 mg of amikacin with 2,000 mg of cefepime, and a third course of 300 mg of amikacin. Each course consisted of four consecutive doses administered every 8 h as 30-min intravenous infusions. Serial plasma and urine samples, which were collected after administration of the fourth dose of each course, were assayed for cefepime and/or amikacin by validated high-performance liquid chromatographic assays. Trough levels of cefepime and amikacin indicated that these antibiotics attained a steady state prior to administration of the fourth dose of each course. Key pharmacokinetic parameters for each antibiotic were determined by noncompartmental methods. The peak concentrations of cefepime and amikacin in plasma when the drugs were given alone were about 160 and 27 ,g/ml, respectively. Levels of each antibiotic in plasma declined, with an apparent half-life of approximately 2.2 h. Urinary recovery of cefepime and amikacin accounted for more than 85% of the administered dose of each antibiotic. Mean renal clearances for cefepime and amikacin ranged from 79 to 95 ml/min and suggested that glomerular filtration is the primary excretion mechanism. The results of the statistical analyses indicated that the pharmacokinetic parameters of cefepime following the concurrent administration of amikacin and following the discontinuation of the amikacin therapy were not significantly altered. Similarly, the pharmacokinetic parameters of amikacin following the concurrent administration of cefepime and following the discontinuation of the cefepime therapy were not significantly altered. Cefepime and amikacin can be coadministered to patients with normal renal function by using the standard recommended dosing regimens.Cefepime (BMY-28142) is a new parenteral cephalosporin with significant potential advantages over other new cephalosporins and nontraditional ,3-lactam antibiotics with respect to its antimicrobial spectrum of activity (12,15). 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). Over 80% of the administered dose of cefepime is recovered in urine in an unchanged form (4, 5, 7-9).In the most severely infected patients, empiric therapy consists of the administration of antibacterial therapy before pathogen identification. The standard approach has been to use an ant...

Pharmacokinetic interactions of ceftazidime, imipenem and aztreonam with amikacin in healthy volunteers

“…These results agree with those of other authors [3] and confirm the absence of significant pharmacokinetic interaction between cefepime and amikacin when co-administered in 16 individuals. The estimated pharmacokinetics for amikacin were similar to those already described (Table 1) whereas glomerular filtration was the main mechanism of excretion for both cefepime and amikacin as also noted in the present study.…”

“…Patients with nosocomial infections are often given a variety of drugs thus raising the question of the existence of any interaction between co-administered ␤-lactams and amikacin. Although one previous study has shown the absence of any pharmacokinetic interaction between cefepime and amikacin [3], the present study aimed to investigate the pharmacokinetic parameters of ceftazidime, imipenem and aztreonam after their intravenous administration singly or in combination with amikacin in healthy volunteers.…”

In vitro Time-Kill Curves of Cefepime and Cef pirome Combined with Amikacin, Gentamicin or Ciprofloxacin against <i>Klebsiella pneumoniae</i> Producing Extended-Spectrum Beta-Lactamase

“…In general, the antibacterial efficacy is greatest with treatment regimens that result in the highest peak concentration in serum and largest area under the serum time-concentration curve [19]. There was no evidence of pharmacokinetic interaction be tween cefepime 2 g and amikacin 300 mg fol lowing concomitant intravenous administra tion of both drugs into contralateral forearm veins of healthy volunteers [20].…”

In Vitro and In Vivo Activities of Amikacin, Cefepime, Amikacin plus Cefepime, and Imipenem against an SHV-5 Extended-Spectrum β-Lactamase-Producing Klebsiella pneumoniae Strain

“…Data from the pharmacokinetic analysis are given in Table 1, except for amikacin plus cefepime because they do not affect the elimination of each other (2).…”

“…The coefficient of variability was Յ5% for each antibiotic assay. The pharmacokinetic values half-life (T 1/2 ), peak concentration (C max ), first occurrence of C max (T max ), area under the concentration-time curve extrapolated to infinity (AUC), and area under the concentration-time curve from 0 to 24 h (AUC 0-24 ) were calculated by a noncompartmental method (2).…”