Aminoglycoside Dosage in Hemodialysis Patients

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Abstract
Regulating aminoglycoside dosage in patients undergoing hemodialysis is difficult because its elimination depends entirely on renal function and because the therapeutic margin is narrow. Guidelines for aminoglycoside dosage were derived from published population‐based kinetics and investigated in a prospective clinical study over a 12‐month period in 50 consecutive patients undergoing hemodialysis with acute (70%) or chronic (30%) renal failure. Based on body weight, each patient received one loading dose (1.5 mg/kg) and a daily maintenance dose (0.5 mg/kg) of netilmicin. The dosage interval was 24 hours. On each hemodialysis day, the dose of netilmicin was given immediately after hemodialysis. Each posthemodialysis dose (1.3 mg/kg) was the sum of the daily maintenance dose plus a supplementary dose to replace the amount of the drug removed during hemodialysis. A blood sample was taken at the start and the end of each hemodialysis and one hour after the start of the posthemodialysis dosage. Netilmicin plasma concentrations were determined by substrate‐labeled fluorescence immunoassay. The mean (± standard deviation) peak plasma concentration of the pooled data for all patients was 7.5 ± 2.7 mg/L, and the mean trough level was 3.6 ± 1.3 mg/L. The theoretically postulated range of therapeutic peak levels (5–10 mg/L) was the same as in patients with normal renal function, whereas the theoretically postulated range of therapeutic trough levels (2.2–5.0 mg/L) was considerably higher than in healthy persons. Peak and trough levels within the postulated range were achieved in 81% of the patients. Peaks and troughs were significantly lower in the 23 patients who did not respond than in the 27 patients who responded to antibiotic treatment (54%). Ototoxicity developed in three of 18 investigated patients (17%). Thus, efficacy and toxicity of aminoglycosides in patients undergoing hemodialysis are comparable with those of patients with normal renal function, and the dosage can be derived from one‐compartment pharmacokinetics.