PULMONARY RETENTION OF FREE AND LIPOSOME-ENCAPSULATED TOBRAMYCIN AFTER INTRATRACHEAL ADMINISTRATION IN UNINFECTED RATS AND RATS INFECTED WITH PSEUDOMONAS-AERUGINOSA

The pulmonary residence time of free and liposome-encapsulated tobramy cin was studied with uninfected rats and rats infected with Psedomonas aeruginosa. Chronic infection in lungs was established by intratrache al administration of 10(8) CPU of P. aeruginosa PA 508 prepared in aga r beads. After 3 days, a single dose (300 mu g) of free or liposome-en capsulated tobramycin was given intratracheally to both infected and u ninfected rats. At various time intervals (0.25 to 16 h) after drug in stillations, the remaining tobramycin was evaluated in blood, lungs, a nd kidneys by a microbiological assay. Intratracheal instillation of l iposome-encapsulated tobramycin resulted in high and sustained levels of tobramycin in lungs of uninfected and infected rats over the 16-h p eriod studied; however, the tobramycin levels were two times higher in uninfected rats. There was no tobramycin detected in the blood or kid neys hom these animals. In contrast, the intratracheally instilled fre e tobramycin was cleared within 3 and 1 h from the lungs of uninfected and infected animals, respectively. These data suggest that the encap sulation of tobramycin in liposomes can result in a significant increa se of its residence time within lungs. This study also shows that pulm onary infection was associated with a lowering of tobramycin levels in lungs.