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...

Serum and urinary levels of cefazolin were determined after a 500-mg parenteral dose in eight azotemic volunteers. The mean peak serum concentration was 1.5 to 5 times the levels obtained in nonazotemic patients. The serum half-life of cefazolin was increased significantly. In patients on dialysis, the mean serum half-life of cefazolin was 4.05 h during (or after) hemodialysis, and 32.1 h during (or after) peritoneal dialysis. There was a significant decrease in cefazolin removal when dialysate flow or membrane surface area of the dialyzer were decreased. It was also shown that one circuit through the dialysis unit caused measurable decrease in cefazolin concentration. These data and previously published reports suggest: (i) the maintenance dose of cefazolin can be decreased in azotemic patients; (ii) patients on hemodialysis will require an additional half dose after dialysis because of efficient removal during hemodialysis; and (iii) patients on peritoneal dialysis do not require an extra dose.Cefazolin, a recently introduced cephalosporin antibiotic, was reported not to be nephrotoxic in recent clinical studies (2, 6, 7). However, this antibiotic produced higher serum levels in uremic than in nonazotemic patients. It was also noted that the serum half-life of cefazolin was reduced by hemodialysis, but was little affected by peritoneal dialysis (1, 3, 5). We have confirmed these results in patients with varying degrees of renal failure and in patients undergoing peritoneal and hemodialysis. We also studied the pharmacokinetics of cefazolin using standard 4-h large-surface-area (2.4 m2) hemodialysis, hemodialysis with reduced membrane surface area, and also the effects of reduced duration of dialysis. MATERIALS AND METHODSEighvruremic patients not on dialysis were given 500 mg of cefazolin as a single intramuscular injection. Serum and urine samples were collected before the injection and at 0.5, 1, 4, 8, 12, and 24 h after administration of the drug.Ten patients on dialysis were divided into three groups. Four patients in Group I were given 1 g of cefazolin intravenously at the initiation of a 4-h hemodialysis by 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. Blood samples were collected serially from venous dialysis lines without anticoagulant, and aliquots of 20 ml were taken from the dialysate for cup-plate assay.

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