Pharmacokinetic and clinical studies with amikacin, a new aminoglycoside antibiotic

Abstract

Pharmacokinetic parameters of amikacin were determined in 12 healthy volunteers after a 1-hr continuous intravenous infusion of 7.5 mg of the drug/kg. The serum concentration rose rapidly to a peak of 37.5 +/- 4.9 mug/ml at the termination of the infusion and declined to 1.3 +/- 0.5 mug/ml 8 hr later. The mean half-life was 114 +/- 16.7 min, and the apparent volume of distribution was 18.1% +/- 1.8% of body weight. During a 4-hr constant intravenous infusion in three subjects, amikacin was cleared from the kidney at a mean rate of 84.3 ml/min per 1.73 m2, and from the serum at a mean rate of 129.7 ml/min per 1.73 m2. Of the administered dose, 93.5% was recovered from the urine in 24 hr (81.7% during the first 6 hr). After single intramuscular injections of 5 mg/kg in 30 patients, serum levels peaked at 1 hr (21.4 +/- 5.4 mug/ml) and declined to 2.4 +/- 0.9 mug/ml by 8 hr. Of 33 patients with serious urinary or bronchopulmonary infections (usually superimposed on chronic organic pathology) treated with amikacin (10 or 15 mg/kg per day for eight to 17 days), 27 had a clinical remission, and in 15 of these patients the pathogen was eradicated.