Anti-tuberculosis activity in the presence of drug resistance as a rationale for prospect use of thiosonide
https://doi.org/10.29001/2073-8552-2020-35-1-125-132
Abstract
Objective. To provide in vitro and in vivo experimental evaluation of the efficacy and tolerability of treatment for multidrugresistant tuberculosis (MDR-TB) with an innovative drug thiosonide.
Material and Methods. The study was performed using M. tuberculosis cultures sensitive to therapy and resistant to isoniazid and rifampicin. A series of experiments using C57Bl/6 mice infected with M. tuberculosis resistant to polychemotherapy (PCT) was performed. The efficacy of treatment of experimental drug-resistant tuberculosis using standard mono- and polychemotherapy regimens with and without drug thiosonide was evaluated.
Results. The study demonstrated in vitro anti-tuberculosis activity of thiosonide including the activity against M. tuberculosis strains resistant to isoniazid and rifampicin. The ability of thiosonide to increase the survival rate of mice infected with MDRTB compared with survival in the presence of traditional chemotherapy was shown. The calculated index of the effectiveness of therapy with the use of anti-tuberculosis drug thiosonide revealed its ability to improve the treatment of experimental MDR-TB. An increase in the mass of experimental animals was observed in the case of therapy with thiosonide, which
indicates good drug tolerability.
Conclusions. Thiosonide, added to the experimental MDR-TB polychemotherapy regimen, increased the treatment efficiency while reducing the number and severity of side effects of pharmacotherapy. This fact makes it possible to consider thiosonide as a promising drug for MDR-TB treatment.
Material and Methods. The study was performed using M. tuberculosis cultures sensitive to therapy and resistant to isoniazid and rifampicin. A series of experiments using C57Bl/6 mice infected with M. tuberculosis resistant to polychemotherapy (PCT) was performed. The efficacy of treatment of experimental drug-resistant tuberculosis using standard mono- and polychemotherapy regimens with and without drug thiosonide was evaluated.
Results. The study demonstrated in vitro anti-tuberculosis activity of thiosonide including the activity against M. tuberculosis strains resistant to isoniazid and rifampicin. The ability of thiosonide to increase the survival rate of mice infected with MDRTB compared with survival in the presence of traditional chemotherapy was shown. The calculated index of the effectiveness of therapy with the use of anti-tuberculosis drug thiosonide revealed its ability to improve the treatment of experimental MDR-TB. An increase in the mass of experimental animals was observed in the case of therapy with thiosonide, which
indicates good drug tolerability.
Conclusions. Thiosonide, added to the experimental MDR-TB polychemotherapy regimen, increased the treatment efficiency while reducing the number and severity of side effects of pharmacotherapy. This fact makes it possible to consider thiosonide as a promising drug for MDR-TB treatment.
About the Authors
A. Yu. Savchenko
Scientific Center for Biomedical Technology of the Federal Medical and Biological Agency
Russian Federation
Russian Federation
Leading Research Scientist, Pharmaceutical Modeling Laboratory
Svetlye Gory Village, Krasnogorsk District, Moscow region, 143442, Russian Federation
M. S. Burenkov
Joint-Stock Company “Pharm-Sintez”
Russian Federation
Russian Federation
Cand. Sci. (Biol.), Manager for Pre-Clinical Research
2, build. 46, Cabelnaya 2nd str., Moscow, 111024, Russian Federation
P. S. Baidin
Joint-Stock Company “Pharm-Sintez”
Russian Federation
Russian Federation
Cand. Sci. (Med.), Head of the Medical Department
2, build. 46, Cabelnaya 2nd str., Moscow, 111024, Russian Federation
G. V. Ramenskaya
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation
Russian Federation
Dr. Sci. (Pharm.), Professor, Director of the Institute of Pharmacy
8, Trubetskaya str., p. 2, Moscow, 119991, Russian Federation
N. V. Perova
Institute for Medical-Biological Research and Technologies
Russian Federation
Russian Federation
Dr. Sci. (Biol.), Deputy Director
43/20, build. 2, B. Tishinsky per., Moscow, 123557, Russian Federation
V. G. Kukes
Clinical Pharmacology Branch Scientific Center for Biomedical Technology of the Federal Medical and Biological Agency
Russian Federation
Russian Federation
Dr. Sci. (Med.), Professor, Full Member of the Russian Academy of Sciences
11, Yauzskaya str., Moscow, 109240, Russian Federation
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Review
For citations:
Savchenko A.Yu., Burenkov M.S., Baidin P.S., Ramenskaya G.V., Perova N.V., Kukes V.G. Anti-tuberculosis activity in the presence of drug resistance as a rationale for prospect use of thiosonide. Siberian Journal of Clinical and Experimental Medicine. 2020;35(1):125-132. (In Russ.) https://doi.org/10.29001/2073-8552-2020-35-1-125-132
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