Distribution and elimination kinetics of intravenously and intramusculary administered tobramycin in man

The pharmacokinetic profile of Tobramycin, a new aminoglycoside antibiotic, has been determined in man following intravenous and intramuscular administration. The serum elimination of the antibiotic obeys two-compartment open model kinetics after intravenous injection. The fast (alpha) and slow (beta) disposition rate constants averaged 0.1169 min-1 and 0.0099 min-1 respectively. The volume of distribution at the steady-state averaged 0.123 liter kg-1 and the plasma clearance 0.8 ml min-1 kg-1. Calculation of the intrinsic absorption rate of an intramuscular dose according to the two-compartment open model indicates that absorption increases during the first 40 minutes, then decreases and is virtually complete 90 minutes after administration in all subjects. The absolute physiological availability of the intramuscular dose averaged 84.9%. A method of administration compatible with the kinetic properties of the drug is proposed.