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Antimicrobial Agents and Chemotherapy, May 1999, p. 1144-1151, Vol. 43, No. 5
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Efficacy of Microencapsulated Rifampin in Mycobacterium tuberculosis-Infected Mice

Debra C. Quenelle,1 Jay K. Staas,2 Gary A. Winchester,2 Esther L. W. Barrow,3 and William W. Barrow3,*

Infectious Disease Animal Models Group,1 Drug Delivery Group,2 and Mycobacteriology Research Unit,3 Southern Research Institute, Birmingham, Alabama

Received 3 September 1998/Returned for modification 25 November 1998/Accepted 5 March 1999

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 replicating Mycobacterium tuberculosis H37Rv, 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 in M. tuberculosis H37Rv 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 log10 reduction 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 log10 units, 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.

* Corresponding author. Mailing address: Mycobacteriology Research Unit, Southern Research Institute, 2000 Ninth Ave. South, Birmingham, AL 35205. Phone: (205) 581-2139. Fax: (205) 581-2877. Email: barrow{at}sri.org.

Antimicrobial Agents and Chemotherapy, May 1999, p. 1144-1151, Vol. 43, No. 5
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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