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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Inhaled large porous particles of capreomycin for treatment of tuberculosis in a guinea pig model
Antimicrobial Agents and Chemotherapy, Volume 51, No. 8, Year 2007
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Description
Capreomycin is used for the treatment of multidrug-resistant tuberculosis (MDR-TB), but it is limited therapeutically by its severe side effects. The objectives of the present studies were (i) to design low-density porous capreomycin sulfate particles for efficient pulmonary delivery to improve local and systemic drug bioavailability and capacity to reduce the bacillary load in the lungs in a manner similar to that achieved with intramuscular injections; (ii) to determine pharmacokinetic parameters after pulmonary administration of these capreomycin particles; and (iii) to evaluate the efficacy of these particles in treating animals in a small-aerosol-inoculum guinea pig model of TB. Capreomycin particles were manufactured by spray drying and characterized in terms of size and drug content. Pharmacokinetic parameters were determined by noncompartmental methods with healthy guinea pigs after administration of capreomycin particles by insufflation. The efficacy of the particles was evaluated by histopathological analysis and in terms of wet organ weight and bacterial burden in TB-infected animals. Lungs of animals receiving a 14.5-mg/kg dose of capreomycin particles showed significantly lower wet weights and smaller bacterial burdens than those of animals receiving any other treatment. These results were supported by histopathological analysis. The feasibility of inhaling capreomycin in a novel powder form, with the ultimate objective of the treatment of MDR-TB, is demonstrated by pharmacokinetic and pharmacodynamic studies with guinea pigs. If applied to humans with MDR-TB, such a therapeutic approach might simplify drug delivery by eliminating injections and might reduce adverse effects through lowering the dose. Copyright © 2007, American Society for Microbiology. All Rights Reserved.
Authors & Co-Authors
García-Contreras, Lucila
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Elbert, Katharina J.
United States, Cambridge
Harvard University
Germishuizen, Willem Andreas
United States, Cambridge
Harvard University
Fourie, P. B.
Unknown Affiliation
Hickey, Anthony James
United States, Chapel Hill
The University of North Carolina at Chapel Hill
Edwards, David A.
United States, Cambridge
Harvard University
Statistics
Citations: 130
Authors: 6
Affiliations: 2
Identifiers
Doi:
10.1128/AAC.01164-06
ISSN:
00664804
Research Areas
Infectious Diseases
Study Locations
Guinea