Safety and Pharmacokinetics of the Substance of the Anti-Smallpox Drug NIOCH-14 after Oral Administration to Laboratory Animals

Safety and Pharmacokinetics of the Substance of the Anti-Smallpox Drug NIOCH-14 after Oral Administration to Laboratory Animals Full article

Journal

Viruses
ISSN: 1999-4915

Output data

Year: 2023, Volume: 15, Number: 1, Article number : 205, Pages count : 22 DOI: 10.3390/v15010205

Tags

orthopoxviruses; anti-smallpox drugs; NIOCH-14; safety; pharmacokinetic

Authors

Shishkina Larisa N ¹ , Mazurkov Oleg Yu. ¹ , Bormotov Nikolai I. ¹ , Skarnovich Maksim O. ¹ , Serova Olga A. ¹ , Mazurkova Natalia A. ¹ , Skarnovich Maria A. ¹ , Chernonosov Alexander А. ² , Selivanov Boris A. ³ , Alexey Ya. Tikhonov ³ , Svetlana G. Gamaley ¹ , Shimina Galina G. ¹ , Sysoyeva Galina M. ¹ , Taranov Oleg S. ¹ , Danilenko Elena D. ¹ , Alexander P. Agafonov ¹ , Maksyutov Rinat А. ¹

Affiliations

1	Federal Budgetary Research Institution—State Research Center of Virology and Biotechnology VECTOR, Federal Service for Surveillance on Consumer Rights Protection and Human Well-Being, 630559 Koltsovo, Russia
2	The Institute of Chemical Biology and Fundamental Medicine, Siberian Branch of the Russian Academy of Sciences, 630090 Novosibirsk, Russia
3	N.N. Vorozhtsov Novosibirsk Institute of Organic Chemistry of the Siberian Branch of Russian Academy of Sciences, 630090 Novosibirsk, Russia

Background: Since most of the modern human population has no anti-smallpox immunity, it is extremely important to develop and implement effective drugs for the treatment of smallpox and other orthopoxvirus infections. The objective of this study is to determine the main characteristics of the chemical substance NIOCH-14 and its safety and bioavailability in the body of laboratory animals. Methods: The safety of NIOCH-14 upon single- or multiple-dose intragastric administration was assessed according to its effect on the main hematological and pathomorphological parameters of laboratory mice and rats. In order to evaluate the pharmacokinetic parameters of NIOCH-14 administered orally, a concentration of ST-246, the active metabolite of NIOCH-14, in mouse blood and organs was determined by tandem mass spectrometry and liquid chromatography. Results: The intragastric administration of NIOCH-14 at a dose of 5 g/kg body weight caused neither death nor signs of intoxication in mice. The intragastric administration of NIOCH-14 to mice and rats at doses of 50 and 150 μg/g body weight either as a single dose or once daily during 30 days did not cause animal death or critical changes in hematological parameters and the microstructure of internal organs. The tissue availability of NIOCH-14 administered orally to the mice at a dose of 50 μg/g body weight, which was calculated according to concentrations of its active metabolite ST-246 for the lungs, liver, kidney, brain, and spleen, was 100, 69.6, 63.3, 26.8 and 20.3%, respectively. The absolute bioavailability of the NIOCH-14 administered orally to mice at a dose of 50 μg/g body weight was 22.8%. Conclusion: Along with the previously determined efficacy against orthopoxviruses, including the smallpox virus, the substance NIOCH-14 was shown to be safe and bioavailable in laboratory animal experiments.

Shishkina L.N. , Mazurkov O.Y. , Bormotov N.I. , Skarnovich M.O. , Serova O.A. , Mazurkova N.A. , Skarnovich M.A. , Chernonosov A.А. , Selivanov B.A. , Alexey Ya. T. , Svetlana G. G. , Shimina G.G. , Sysoyeva G.M. , Taranov O.S. , Danilenko E.D. , Alexander P. A. , Maksyutov R.А.
Safety and Pharmacokinetics of the Substance of the Anti-Smallpox Drug NIOCH-14 after Oral Administration to Laboratory Animals
Viruses. 2023. V.15. N1. 205 :1-22. DOI: 10.3390/v15010205 WOS Scopus OpenAlex

Web of science:	WOS:000918694000001
Scopus:	2-s2.0-85147045433
OpenAlex:	W4315574219

DB	Citing
OpenAlex	6
Scopus	6
Web of science	6