Pharmacokinetic and Clinical Studies with Amikacin, a New Aminoglycoside Antibiotic

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...

Section: Resultssupporting

confidence: 89%

Lack of pharmacokinetic interaction between cefepime and amikacin in humans

Barbhaiya

Knupp

Pfeffer

et al. 1992

“…Studies of pharmacokinetic properties of amikacin in adults have shown the volume of distribution to be 0.25 liter/kg, which is similar to the Vd we found (3,4,6,11,16,18). A previous study of amikacin in pediatric patients revealed a Vd of 0.32 liter/kg, but this higher value probably was due to the inclusion of a large number of patients with cystic fibrosis, who have abnormal weight-to-surface area ratios (25).…”

supporting

confidence: 83%

“…A previous study of amikacin in pediatric patients revealed a Vd of 0.32 liter/kg, but this higher value probably was due to the inclusion of a large number of patients with cystic fibrosis, who have abnormal weight-to-surface area ratios (25). The differences in the clinical pharmacology between our pediatric patients and adults can be accounted for by the significantly greater total body clearance of amikacin (131 versus 100 ml/min per 1.73 m2) and shorter half-life (1.24 h in children versus 2.2 h in adults) (3,4,6,11,16,18).…”

mentioning

confidence: 98%

“…It is effective in the treatment of patients with serious infections due to gram-negative bacilli and is particularly useful in therapy of infections involving organisms that are resistant to other aminoglycoside antibiotics (1,21). Pharmacokinetic data related to its use in adults (3,4,6,11,16,18) and neonates (5,12,22) are available; however, infornation supporting the recommended dose and frequency ofadministration for older infants and children is scant (15,25). We evaluated pharmacokinetic parameters and toxicity in 50 pediatric patients who ,ug/ml for group I; 18.1 ± 3.2 lAg/ml for group II; and 17.2 + 1.7 ug/ml for group IH.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Amikacin pharmacokinetics in pediatric patients with malignancy

Cleary¹,

Pickering²,

Kramer³

et al. 1979

The pharmacokinetics of anmikacin were evaluated in 50 pediatric patients (1 to 17 years of age) with malignancies and nonnal renal function. Dosage regimens of 5 mg/kg per dose were administered intravenously (i) over 30 min every 8 h, (ii) over 60 min every 8 h, and (iii) over 60 min every 6 h. Administration of amikacin over 30 mim produced concentrations in serum of 29.3 ± 5.7 jig/ml at the end of the infusion and subtherapeutic concentrations 4 h after the infusion. The regimen of 20 mg/kg per 24 h, divided into doses given every 6 h infused over 60 min, achieved concentrations in serum at the end of the infusion of 17.2 ± 1.7 jsg/ml and at 6 h of 1.2 ± 0.3 ,ug/ml. The serum half-life was 1.24 ± 0.09 h, volume of distribution was 0.26 ± 0.02 liter/kg, and total body clearance rate was 131 ± 10 ml/min per 1.73 m2. No accumulation of amnikacin was noted, and no significant side effects could be attributed to the drug. This study suggests that the optimal initial dosage regimen of amikacin in children is 20 mg/kg per 24 h administered in equal doses every 6 h over 60 min; however, optimal therapy requires individualization of dosage based on measured serum concentrations and susceptibility data on bacterial pathogens isolated.

“…Amikacin, another recently developed semisynthetic aminoglycoside, has proven effective in treatment of various infections, and its toxicity seems to be similar to that of gentamicin (3,6,10 12 h for 7 to 10 days. All patients had complicated urinary tract infections, mainly due to obstruction of the lower urinary tract from benign hyperplasia, prostate or bladder carcinoma, or urethral stricture.…”

mentioning

confidence: 99%

Comparison of Netilmicin and Amikacin in Treatment of Complicated Urinary Tract Infections

Maigaard

Frimodt‐Møller

Madsen

1978

Netilmicin and amikacin, two recently developed aminoglycosides, were compared in a prospective, randomized study of 57 male patients with complicated urinary tract infections. Both drugs were administered intramuscularly every 12 h for 7 to 10 days, netilmicin at 2 mg/kg and amikacin at 7.5 mg/kg. The two groups were comparable as to infecting bacteria and underlying pathology of the urinary tract. No patients had indwelling catheters. All microorganisms isolated were sensitive to both antibiotics. A total of 69% of the patients treated with netilmicin and 57% of the patients treated with amikacin were cured of the infection, as defined by a negative culture at 7 days after discontinuation of treatment. No major side effects were recorded, and no significant changes were noted in parameters of renal function. Of the patients treated with amikacin, 21% experienced temporary local pain at the injection site; no such effect was noted in the netilmicin-treated group. Therefore, netilmicin appeared to be as effective and better tolerated than did amikacin in the treatment of complicated urinary tract infection.