[Pharmacokinetic studies of tobramycin using the continuous intravenous infusion method (author's transl)]

Tobramycin (TOB) was administered to 4 healthy adult volunteers (mean body weight 63.5 kg, surface area 1.71 m2) as one time 90 mg dose by intramuscular injection or by intravenous infusion (30 or 60 minutes) in a crossover study. Serum and urinary concentrations were assayed by bioassay and radioimmunoassay (RIA). Pharmacokinetic analysis was done with a one-compartment open model in the case of intramuscular injection and a two-compartment open model in the case of intravenous infusion. The correlation constant was 0.92, and the relation formula was y = 0.81x+0.13 between bioassay and RIA. In the case of intramuscular injection, the peak serum concentration was 5.1 approximately 6.3 mcg/ml (mean 5.3 mcg/ml), and values calculated with pharmacokinetic parameters from the mean serum concentration were Tmax = 0.745 hour, Cmax = 5.34 mcg/ml and half life (T1/2) = 89.6 minutes. With 60 minutes intravenous infusion, the peak serum concentration was 6.7 approximately 9.1 mcg/ml (mean 7.5 mcg/ml), and the calculated value was 7.63 mcg/ml. The value after 2 hours was nearly equal to those for intramuscular injection. T 1/2 of beta-phase was 95.8 minutes. With 30 minutes intravenous infusion, the peak serum concentration was 8.4 approximately 11.8 mcg/ml (mean 10.2 mcg/ml), and the calculated value was 9.81 mcg/ml. T 1/2 of beta-phase was 105.3 minutes and the serum concentration of the beta-phase was same as that for intramuscular injection administration after 6 hours. We concluded that 60 minutes intravenous infusion of TOB 90 mg is more effective and safe than the 30 minutes method from the standpoint of toxicity, and the serum concentration of the beta-phase is similar to that with intramuscular injection. With each administration method, urinary recovery was 70 approximately 80% for 8 hours.