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Antimicrobial Agents and Chemotherapy, May 1999, p. 1144-1151, Vol. 43, No. 5
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.
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Efficacy of Microencapsulated Rifampin in
Mycobacterium tuberculosis-Infected Mice
*
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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