PULMONARY RETENTION OF FREE AND LIPOSOME-ENCAPSULATED TOBRAMYCIN AFTER INTRATRACHEAL ADMINISTRATION IN UNINFECTED RATS AND RATS INFECTED WITH PSEUDOMONAS-AERUGINOSA
PULMONARY RETENTION OF FREE AND LIPOSOME-ENCAPSULATED TOBRAMYCIN AFTER INTRATRACHEAL ADMINISTRATION IN UNINFECTED RATS AND RATS INFECTED WITH PSEUDOMONAS-AERUGINOSA
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DOI：
10.1128/aac.38.5.1090
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发表时间：
1994-05-01
影响因子：
4.9
通讯作者：
LAGACE, J
中科院分区：
文献类型：
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作者：
OMRI, A;BEAULAC, C;LAGACE, J
用未感染的大鼠和感染铜绿假单胞菌的大鼠研究了游离和脂质体包封的妥布霉素的肺滞留时间。通过鼻内给予在琼脂珠中制备的10（8）CPU铜绿假单胞菌PA 508，建立肺部慢性感染。3天后，向感染和未感染的大鼠气管内给予单剂量（300 μ g）游离或脂质体包裹的妥布霉素。在药物滴注后的不同时间间隔（0.25至16 h），通过微生物测定法评价血液、肺和肾脏中的剩余妥布霉素。肠内滴注脂质体包封的妥布霉素导致在高和持续的妥布霉素水平在肺中的未感染和感染的大鼠超过16小时的研究期间，然而，妥布霉素水平的两倍高未感染的大鼠。在这些动物的血液或肾脏中未检出妥布霉素。相反，气管内滴注的游离妥布霉素分别在3和1 h内从未感染和感染动物的肺部清除。这些数据表明妥布霉素在脂质体中的包封可导致其在肺内的停留时间显著增加。这项研究还表明，肺部感染与肺中妥布霉素水平降低有关。
The pulmonary residence time of free and liposome-encapsulated tobramycin was studied with uninfected rats and rats infected with Psedomonas aeruginosa. Chronic infection in lungs was established by intratracheal administration of 10(8) CPU of P. aeruginosa PA 508 prepared in agar beads. After 3 days, a single dose (300 mu g) of free or liposome-encapsulated tobramycin was given intratracheally to both infected and uninfected rats. At various time intervals (0.25 to 16 h) after drug instillations, the remaining tobramycin was evaluated in blood, lungs, and kidneys by a microbiological assay. Intratracheal instillation of liposome-encapsulated tobramycin resulted in high and sustained levels of tobramycin in lungs of uninfected and infected rats over the 16-h period studied; however, the tobramycin levels were two times higher in uninfected rats. There was no tobramycin detected in the blood or kidneys hom these animals. In contrast, the intratracheally instilled free tobramycin was cleared within 3 and 1 h from the lungs of uninfected and infected animals, respectively. These data suggest that the encapsulation of tobramycin in liposomes can result in a significant increase of its residence time within lungs. This study also shows that pulmonary infection was associated with a lowering of tobramycin levels in lungs.