Efficacy and safety of aminoglycosides once-a-day: experimental and clinical data.

Scand J Infect Dis Suppl

Laboratory of Physiological Chemistry, Catholic University of Louvain, Belgium.

Published: July 1991

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In vitro and animal data show that the efficacy of an aminoglycoside is primarily related to its serum peak levels and AUC, whereas its toxicity is critically dependent upon the schedule of the administration of the daily dose as well as the duration of the treatment and the total amount of drug administered. The reduction of toxicity by intermittent dosing, e.g. once-a-day dosing (q.d.) versus splitting the daily dose in multiple administrations is connected with the saturable character of the aminoglycoside transport within inner ear and renal tissues. Clinical trials have been conducted in various types of infections in order to investigate the efficacy and tolerance of aminoglycosides q.d. Using conventional criteria of evaluation, this mode of administration was found to be equally efficacious and marginally less toxic than aminoglycosides in conventional dosing regimens. We have studied the pharmacokinetics and the early signs of renal (phospolipiduria) and auditory (high frequency audiometry) alterations of aminoglycosides given q.d. and by conventional dosage schedules to patients with pelvic inflammatory disease. It was shown that netilmicin and amikacin were better tolerated q.d. than after t.i.d. or b.i.d. administration. In addition, amikacin induced less alterations than netilmicin.

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