The half-life of amikacin after a single intramuscular injection was determined in patients with severe renal failure who received 3.75 mg of drug/kg and in patients with various degrees of renal function who received 7.5 mg of drug/kg. The relation of the half-life of amikacin to levels of serum creatinine is practically identical to that of kanamycin. However, although concentrations of serum creatinine remained practically unchanged, rates of creatinine clearance may by considerably decreased in older subjects. This decrease may result in overestimation of the rate of glomerular filtration and subsequent overdosage. Therefore, the half-life of amikacin should be derived from values of rates of creatinine clearance or be predicted with use of a nomogram. The calculated half-life values may be used for development of appropriate dosage schedules for patients with various degrees of renal function. Such schedules would ensure therapeutic levels of drug and avoid potentially toxic accumulation of antibiotic.
The hypothesis that the pharmacokinetics of amikacin are more predictable than those of gentamicin or tobramycin was studied. In a three-way crossover design 58 volunteers received 7.5 mg/kg amikacin by iv infusion and either 1.5 mg/kg or 1 mg/kg gentamicin and tobramycin. The mean half-life and mean serum concentration at 1 h for each drug was determined. No consistent significant difference was found between the pharmacokinetics of amikacin and the other two drugs.
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