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Increase of amikacin half-life during therapy in patients with renal insufficiency

Serum kinetics of amikacin were investigated in 17 severely ill patients. During both the first and last dose intervals of therapy, the serum concentration time course of every patient was documented by 17 blood samples. Six of the patients had moderate to severe renal insufficiency (serum creatinine greater than 1.5 mg/100 ml). In this group of patients, a pronounced rise in serum half-life of amikacin was observed, increasing from a mean of 11.2 to 21.5 h for the first and last interval, respectively. In contrast, mean half-life remained stable in the group of 11 patients with normal renal function. No change in mean serum creatinine occurred in either group, when data from the beginning and the end of therapy were compared. Therefore, the increase of amikacin half-life is apparently not due to a reduction of the glomerular filtration rate, but rather to a decrease of the ratio of amikacin to creatinine clearance. Indeed, a significant reduction of this ratio could be shown in the seven patients in which 24-h creatinine clearance was determined during the first and last day of therapy. This phenomenon is discussed in the context of aminoglycoside accumulation in deep compartments. We conclude that the daily dose of amikacin has to be reduced during therapy in patients with impaired, but stable, renal function.