Efficacy of microencapsulated rifampin in Mycobacterium tuberculosis-infected mice.
Efficacy of microencapsulated rifampin in Mycobacterium tuberculosis-infected mice.
复制标题
微囊利福平对结核分枝杆菌感染小鼠的功效。
DOI：
10.1128/aac.43.5.1144
复制
发表时间：
1999
影响因子：
4.9
通讯作者：
Barrow,WW
中科院分区：
文献类型：
--
作者：
Quenelle,DC;Staas,JK;Winchester,GA;Barrow,EL;Barrow,WW
Rifampin is a first-line drug useful in the treatment of tuberculosis. By using biocompatible polymeric excipients of lactide and glycolide copolymers, two microsphere formulations were developed for targeted and sustained delivery of rifampin, with minimal dosing. A small-microsphere formulation, with demonstrated ability to inhibit intracellularly replicatingMycobacterium tuberculosisH37Rv, was tested along with a large-microsphere formulation in an infected mouse model. Results revealed that by using a single treatment of the large-microsphere formulation, it was possible to achieve a significant reduction inM. tuberculosisH37Rv CFUs in the lungs of mice by 26 days postinfection. A combination of small (given as two injections on day 0 and day 7) and large (given as one injection at day 0) rifampin-loaded microsphere formulations resulted in significant reductions in CFUs in the lungs by 26 days, achieving a 1.23 log10reduction in CFUs. By comparison, oral treatment with 5, 10, or 20 mg of rifampin/kg of body weight, administered every day, resulted in a reduction of 0.42, 1.7, or 1.8 log10units, respectively. Thus the microsphere formulations, administered in one or two doses, were able to achieve results in mice similar to those obtained with a daily drug regimen within the range of the highest clinically tolerated dosage in humans. These results demonstrate that microsphere formulations of antimycobacterial drugs such as rifampin can be used for therapy of tuberculosis with minimal dosing.
