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To determine the pharmacokinetics and efficacy of tobramycin against pulmonary infections of Pseudomonas aeruginosa in rats after intratracheal administration of conventional and liposomal formulations.Male Sprague–Dawley rats were inoculated with 106 cfu of a mucoid variant of P. aeruginosa (MIC of tobramycin for PA 508=1 mg/L) and tobramycin (conventional or liposomal formulations) was administered in single (490 µg) and multiple dose (490 µg during 4 days) experiments. Rats were killed at multiple time points to determine the residual cfu of P. aeruginosa and tobramycin amounts in lungs. Pharmacokinetic parameters were calculated using a two-compartment model with NONMEM.Mean (±S.D.) elimination half-life (t1/2β) and pulmonary exposure (AUC) of the conventional formulation were 14.0 ±4.0 h and 663 ±89 µg×h/lungs, respectively. The pharmacokinetic profile of liposomal tobramycin was markedly different, with a longer t1/2β (34.4 ±5 h, P < 0.05), resulting in an increased AUC (3890 ±560 µg×h/lungs, P < 0.05). χ2 analyses were carried out on cfu data distributed in the following categories: below 103, 103–105, and above 105 cfu. In the single dose experiments, approximately 90% of the observations were above 105 cfu for both formulations. Significant differences in cfu distribution were observed after multiple treatments, with approximately 10% of the observations falling below 103 cfu of P. aeruginosa for the conventional formulation versus 30% for the liposomal formulation.The liposomal formulation of tobramycin promoted drug retention in lungs and improved its efficacy after multiple treatments.