Comparative clinical pharmacology of gentamicin, sisomicin, and tobramycin

Abstract

Using a randomized crossover design involving 12 normal subjects, we studied comparatively the pharmacokinetics and tolerance of three aminoglycoside antibiotics, gentamicin, sisomicin, and tobramycin. Serum concentrations were determined during 8 h and the urine recovery rate was determined within 24 h after a 1-h intravenous infusion of the respective antibiotic in a dose of 1 mg/kg of body weight. Microbiological assay was performed with the agar diffusion test (Bacillus subtilis); pharmacokinetic calculations were performed by means of a digital computer on the basis of a mathematical model of an open, two-compartment system. Of the three antibiotics studied, gentamicin showed the lowest concentration in serum after termination of the 1-h infusion (3.85 +/- 0.67 mug/ml), and the serum-regression curve steadily lay below those of the two other antibiotics. Sisomicin had the highest serum concentrations (4,66 +/- 1.24 mug/ml) and the serum-level curve exceeded that of the two other antibiotics. Tobramycin occupied a position between sisomicin and gentamicin in form of its serum level characteristics. Corresponding to the serum kinetics we also found slight differences in the pharmacokinetic parameters, especially in serum half-lives, elimination constants, and areas under the serum level curves. The test of liver and kidney functions and the hematological systems, as well as the function of the stato-acusticus nerve, showed no pathological changes by any of the three antibiotics tested.