Experimental Pharmacokinetics, Metabolism and Tissue Distribution Studies Fluorothiazinon, a of Novel Antivirulence Drug
https://doi.org/10.33647/2074-5982-19-1-73-84
Abstract
We studied the pharmacokinetics, tissue availability and metabolism of fluorothiazinon, a novel antivirulence drug, in mouse blood, liver, kidneys and lungs by administering the substance intragastrically at dose of 400 mg/kg. Fluorothiazinon was established to exhibit good tissue availability and long residential time. This drug is metabolized mainly by glucuronidation.
Supporting agencies: the work was funded by the Ministry of Science and Higher Education of the Russian Federation within the framework of state support for the creation and development of a World-Class Research Centers “Digital Biodesign and Personalized Healthcare” No. 075-15-2022-304
About the Authors
M. V. Savitskii
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation
Russian Federation
Mark V. Savitskii
119991, Moscow, Trubetskaya Str., 8, build. 2
N. E. Moskaleva
I.M. Sechenov First Moscow State Medical University (Sechenov University); World-Class Research Centers of Digital Biodesign and Personalized Healthcare, I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation
Russian Federation
Natalia E. Moskaleva, Cand. Sci. (Biol.)
119991, Moscow, Trubetskaya Str., 8, build. 2;
N. A. Zigangirova
National Research Center for Epidemiology and Microbiology named after N.F. Gamaleya of the Ministry
of Health Care of Russia
Russian Federation
Russian Federation
Nailya A. Zigangirova, Dr. Sci. (Biol.)
123098, Moscow, Gamalei Str., 18
A. V. Soloveva
National Research Center for Epidemiology and Microbiology named after N.F. Gamaleya of the Ministry
of Health Care of Russia
Russian Federation
Russian Federation
Anna V. Soloveva
123098, Moscow, Gamalei Str., 18
A. B. Sheremet
National Research Center for Epidemiology and Microbiology named after N.F. Gamaleya of the Ministry
of Health Care of Russia
Russian Federation
Russian Federation
Anna B. Sheremet, Cand. Sci. (Biol.)
123098, Moscow, Gamalei Str., 18
N. E. Bondareva
National Research Center for Epidemiology and Microbiology named after N.F. Gamaleya of the Ministry
of Health Care of Russia
Russian Federation
Russian Federation
Natalia E. Bondareva, Cand. Sci. (Med.)
123098, Moscow, Gamalei Str., 18
N. L. Lubenec
National Research Center for Epidemiology and Microbiology named after N.F. Gamaleya of the Ministry
of Health Care of Russia
Russian Federation
Russian Federation
Nadezhda L. Lubenec
123098, Moscow, Gamalei Str., 18
N. V. Pyatigorskaya
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation
Russian Federation
Natalia V. Pyatigorskaya, Corresponding Member of the RAS, Dr. Sci. (Pharm.), Prof.
119991, Moscow, Trubetskaya Str., 8, build. 2
S. A. Appolonova
I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation
Russian Federation
Svetlana A. Appolonova, Cand. Sci. (Chem.)
119991, Moscow, Trubetskaya Str., 8, build. 2
References
1. Bondareva N.E., Soloveva A.V., Sheremet A.B., Koroleva E.A., Kapotina L.N., Morgunova E.Y., Luyksaar S.I., Zayakin E.S., Zigangirova N.A. Preventative treatment with Fluorothiazinon suppressed Acinetobacter baumannii-associated septicemia in mice. J. Antibiot. (Tokyo). 2022;75(3):155–163. DOI: 10.1038/s41429-022-00504-y.
2. Calvert M.B., Jumde V.R., Titz A. Pathoblockers or antivirulence drugs as a new option for the treatment of bacterial infections. Beilstein J. Org. Chem. 2018;14:2607–2617. DOI: 10.3762/bjoc.14.239.
3. Godfrey K.R., Arundel P.A., Dong Z., Bryant R. Modelling the Double Peak Phenomenon in pharmacokinetics. Comput. Methods Programs Biomed. 2011;104(2):62–69. DOI: 10.1016/j. cmpb.2010.03.007.
4. Koroleva E.A., Kobets N.V., Zayakin E.S., Luyksaar S.I., Shabalina L.A., Zigangirova N.A. Small molecule inhibitor of type three secretion suppresses acute and chronic Chlamydia trachomatis infection in a novel urogenital Chlamydia model. Biomed Res. Int. 2015; 2015: 484853. DOI: 10.1155/2015/484853.
5. Murakami T. Absorption sites of orally administered drugs in the small intestine. Expert Opin. Drug Discov. 2017;12(12):1219–1232. DOI: 10.1080/17460441.20 17.1378176.
6. Nesterenko L.N., Zigangirova N.A., Zayakin E.S., Luyksaar S.I., Kobets N.V., Balunets D.V., Shabalina L.A., Bolshakova T.N., Dobrynina O.Y., Gintsburg A.L. A small-molecule compound belonging to a class of 2,4-disubstituted 1,3,4-thiadiazine-5-ones suppresses Salmonella infection in vivo. J. Antibiot. (Tokyo). 2016;69(6):422–427. DOI: 10.1038/ja.2015.131.
7. Ogawara H. Possible drugs for the treatment of bacterial infections in the future: Anti-virulence drugs. J. Antibiot. (Tokyo). 2021;74(1):24–41. DOI: 10.1038/ s41429-020-0344-z.
8. Ogungbenro K., Pertinez H., Aarons L. Empirical and semi-mechanistic modelling of double-peaked pharmacokinetic profile phenomenon due to gastric emptying. AAPS J. 2015;17(1):227–336. DOI: 10.1208/ s12248-014-9693-5.
9. Roberts M.S., Magnusson B.M., Burczynski F.J., Weiss M. Enterohepatic circulation. Clin. Pharmacokinet. 2002;41(10):751–790. DOI: 10.2165/00003088- 200241100-00005.
10. Shang E., Xiang B., Liu G., Xie S., Wei W., Lu J. Determination of phenazopyridine in human plasma via LC-MS and subsequent development of a pharmacokinetic model. Anal. Bioanal. Chem. 2005;382(1):216– 222. DOI: 10.1007/s00216-005-3197-1.
11. Sheremet A.B., Zigangirova N.A., Zayakin E.S., Luyksaar S.I., Kapotina L.N., Nesterenko L.N., Kobets N.V., Gintsburg A.L. Small molecule inhibitor of type three secretion system belonging to a class 2,4-disubstituted-4H-[1,3,4]-thiadiazine-5-ones improves survival and decreases bacterial loads in an airway Pseudomonas aeruginosa infection in mice. Biomed. Res. Int., 2018:5810767. DOI: 10.1155/2018/5810767.
12. Zigangirova N.A., Kost E.A., Didenko L.V., Kapotina L.N., Zayakin E.S., Luyksaar S.I., Morgunova E.Y., Fedina E.D., Artyukhova O.A., Samorodov A.V., Kobets N.V. A small-molecule compound belonging to a class of 2,4-disubstituted 1,3,4-thiadiazine-5-ones inhibits intracellular growth and persistence of Chlamydia trachomatis. J. Med. Microbiol. 2016;65(1):91–98. DOI: 10.1099/jmm.0.000189.
13. Zigangirova N.A., Nesterenko L.N., Sheremet A.B., Soloveva A.V., Luyksaar S.I., Zayakin E.S., Balunets D.V., Gintsburg A.L. Fluorothiazinon, a small-molecular inhibitor of T3SS, suppresses salmonella oral infection in mice. J. Antibiot. (Tokyo). 2021;74(4):244–254. DOI: 10.1038/s41429-020- 00396-w.
14. Zigangirova N.A., Zayakin E.S., Kapotina L.N., Kost E.A., Didenko L.V., Davydova D.Y., Rumyanceva J.P., Gintsburg A.L. Development of chlamydial type III secretion system inhibitors for suppression of acute and chronic forms of chlamydial infection. Acta Naturae. 2012;4(2):87–97.
Review
For citations:
Savitskii M.V., Moskaleva N.E., Zigangirova N.A., Soloveva A.V., Sheremet A.B., Bondareva N.E., Lubenec N.L., Pyatigorskaya N.V., Appolonova S.A. Experimental Pharmacokinetics, Metabolism and Tissue Distribution Studies Fluorothiazinon, a of Novel Antivirulence Drug. Journal Biomed. 2023;19(1):73-84. (In Russ.) https://doi.org/10.33647/2074-5982-19-1-73-84
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