New schedule for tobramycin administration.

Ten patients received a loading dose of tobramycin of 60 mg/m2 intravenously over 0.5 h followed immediately by 60 mg/m2 over 2 h every 4 h. The highest mean serum concentration (at the end of the loading dose) was 6.0 +/- 0.3 microgram/ml (range, 3.2 to 10.9 microgram/ml). The mean serum concentration 2 h after the end of the initial 2-h infusion was 3.0 +/- 0.2 microgram/ml (range, 1.6 to 3.9 microgram/ml). This schedule of tobramycin was used to treat 117 patients with presumed or proven infection. There were no differences in the mean serum concentrations of tobramycin at comparable times on days 3 to 4 and 6 to 7. Only 60% of patients had serum levels between 3 micrograms/ml (trough) and 10 micrograms/ml (peak). This intermittent schedule of administration resulted in substantial fluctuations in serum concentrations of tobramycin and produced trough concentrations which were too low or peak concentrations which were too high in some patients.