Effect of Renal Failure and Dialysis on the Serum Concentration of the Aminoglycoside Amikacin

Abstract

Serum and dialysate levels of amikacin were determined at appropriate intervals after a 300-mg intravenous dose as a continuous infusion in six patients with end-stage renal failure undergoing hemodialysis and in three patients on peritoneal dialysis. The mean serum half-life of amikacin was 3.75 h during (or after) hemodialysis and 29 h during (or after) peritoneal dialysis. Although not on hemodialysis in the same six patients, the serum half-life was 28 h. The results indicate that the maintenance dose of amikacin should be markedly decreased in patients with severe renal failure even ifthey are treated with peritoneal dialysis, and that serial serum antibiotic concentrations are essential to prevent cumulative toxicity of the drug.Amikacin is a new aminoglycoside antibiotic with an antibacterial spectrum comparable to gentamicin and tobramycin (3, 4). Since aminoglycosides are excreted mainly through the kidney and not metabolized in the body, their toxic effects are increased in renal failure. However, these antibiotics may be the only available agents to treat life-threatening infections. It, therefore, is important to know how renal failure and renal dialysis effect the pharmacology of amikacin. We accordingly determined the serum concentration, half-life, and dialysate concentration of amikacin in patients with renal failure who were being dialyzed, and the results are the subject of this report.MATERIALS AND METHODS Patient selection. Studies were performed in six patients undergoing a 4-h hemodialysis using two Cordis-Dow model no. 4 hollow fiber kidneys. Blood flow during dialysis was approximately 200 ml/min, and dialysate flow was 500 ml/min. Three patients who were being treated with peritoneal dialysis using Impersol solution run at 2 liters/h for 48 h were studied. The patients had stable creatinine clearance values below 10 mg/min.Patients with congestive heart failure, concurrent hepatic disease, and acute blood loss were excluded from this study. The age, sex, body weight, serum creatinine, total protein, and serum albumin levels in six patients with end-stage renal disease on hemodialysis are summarized in Table 1. All patients were evaluated before and 1 week after amikacin administration for adverse effects, and no changes were found in the histories and physical examinations, blood count, urinalysis, bilirubin, serum glutamic oxalacetic transaminase, alkaline phosphatase, serum protein, serum albumin, creatinine, blood urea nitrogen, and serum electrolytes.Collection of specimens. Patients on hemodialysis. A single dose of 300 mg of amikacin was administered intravenously (i.v.) over a period of 60 min starting 75 min before the onset of dialysis. Blood samples were drawn at the beginning of dialysis and thereafter at 5, 30, 90, 210, and 270 min and 12 and 24 h. The dialysate was collected and pooled. Volumes were measured, and a 20-ml sample was taken for antibiotic assay and then frozen immediately. The same dose of amikacin was given 10 to 14 days later to the same six patients on a day...

Amikacin Therapy of Serious Gram-Negative Bacillary Infections in Chronic Hemodialysis Patients

“…The high therapeutic ratio achieved with amikacin and noted in our patients (except in the one in whom resist ant P. aeruginosa emerged) obviates the need for an additional dose before dialysis. On the contrary, the relatively low clear ance of amikacin during hemodialysis in our patients (mean post/predialysis levels = 61.5% with a range from 46.2 to 74.0%), and also noted in volunteers [14] indicate that the doses after the initial dose should be decreased. The importance of adjusting doses according to results of readily availa ble results of serum assay determinations for amikacin cannot be overemphasized.…”

“…They showed that the mean half-life of ami kacin during hemodialysis in Cordis-Dow hollow fiber dialyzers was 3.75 h and recom mended reducing doses after hemodialysis [14]. 4 of our patients maintained thera peutic levels of amikacin with a reduction of dosage administered after hemodialysis.…”

“…Madhawan et al [14] reported data on clearance of amikacin in 6 patients without infection who were given amikacin during chronic hemodialysis and noted that the maintenance dose of amikacin should be markedly reduced during hemodialysis but did not make specific recommendations [14]. The present study reports the efficacy and toxicity of amikacin in therapy of 7 gram-negative bacillary infections occurring during hemodialysis in 6 patients and also makes recommendations for dosages of ami kacin in chronic hemodialysis patients.…”

“…Madhawan et al [14] used a schedule of administration which was different from ours and gave amikacin to 6 volunteers. They showed that the mean half-life of ami kacin during hemodialysis in Cordis-Dow hollow fiber dialyzers was 3.75 h and recom mended reducing doses after hemodialysis [14].…”

“…Based upon the aggregate of experience with kanamycin, the observations of Mad hawan et al [14] in volunteers with amika cin and our experience with amikacin, the following recommendations are made for the use of amikacin in patients undergoing chronic hemodialysis. The first dose should be the normal dose of 7.5 mg/kg.…”