Efficacy of an Intravenous Form of Rifapentine in a Model of Experimental Tuberculosis in Mice

Solubilization of rifapentine with human serum albumin (HSA) was used to produce a water-miscible form consisting of a colloidal suspension of particles of size 538 ± 9 nm. Dilution of the suspension more than 20-fold led to dissociation of the aggregates formed during solubilization procedure, prod...

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Bibliographic Details
Published in:Pharmaceutical chemistry journal 2017-10, Vol.51 (7), p.616-621
Main Authors: Ostrovskii, K. P., Osipova, N. S., Vanchugova, L. V., Shipulo, E. V., Potapov, V. D., Pereverzeva, É. R., Treshchalin, I. D., Maksimenko, O. O., Gel’perina, S. É.
Format: Article
Language:English
Subjects:
Albumin
Analysis
Fluorescence
Medicine
Organic Chemistry
Pharmacology/Toxicology
Pharmacy
Tuberculosis
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Summary:Solubilization of rifapentine with human serum albumin (HSA) was used to produce a water-miscible form consisting of a colloidal suspension of particles of size 538 ± 9 nm. Dilution of the suspension more than 20-fold led to dissociation of the aggregates formed during solubilization procedure, producing a transparent solution. This was associated with a reduction in particle size to 10 – 20 nm, corresponding to the particle size in HSA solution at the same concentration. A fluorescence method showed that suspensions contained both free rifapentine and its complex with HSA. Studies of the activity against the pathogen of tuberculosis, Mycobacterium tuberculosis H37Rv, in a model of acute infection in Balb/c mice showed that the water-miscible form of rifapentine given intravenously had high activity against mycobacteria, comparable with the activity of rifapentine substance, decreasing mycobacterial loadings in the parenchymatous organs from 10 6 – 10 7 to 10 2 – 10 3 cfu/organ. Thus, use of HSA as solubilizer yielded an intravenous form of rifapentine retaining the activity of the antibiotic against Mycobacterium tuberculosis.
ISSN:0091-150X
1573-9031
DOI:10.1007/s11094-017-1663-7