Investigation of the Therapeutic Effect of Tobramycin in Mice with Experimental Pneumonia in One-shot Versus Divided-dose Schedules
We measured the plasma levels of tobramycin administered by different methods and evaluated the therapeutic effects of tobramycin in mice with experimental pneumonia in various methods and dose schedules. (1) Mice were dosed with tobramycin intramuscular, intravenous oneshot injection and drip infusion, and intramuscular injection in divided doses at intervals of 15 minutes. The plasma concentration of the drug was determined at timed intervals after administration in each instance. Intramuscular and one-shot intravenous injections resulted in substantially parallel time courses of plasma concentration and plasma concentration with drip infusion was similar to that after divided intramuscular injection. (2) A therapeutic experiment was conducted in mice with Klebsiella pneumoniae pneumonia using one-shot and divided intramuscular injection methods of tobramycin. The one-shot injection group showed a satisfactory result at the dose level of 2 mg/kg, but the injection in four divided doses yielded better results at 1 mg/kg. Therefore, in cases where high doses are not feasible or are undesirable, the time of contact of the bacteria and the drug should be prolonged, rather than trying to increase the peak plasma concentration of the drug.