Estimation of Absolute Bioavailability of the Chemical Substance of the Anti-Smallpox Preparation NIOCH-14 in Mice
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Absolute Bioavailability of the Chemical Substance of the Anti-Smallpox Preparation NIOCH-14 in Mice O. Yu. Mazurkov1, L. N. Shishkina1, N. I. Bormotov1, M. O. Skarnovich1, O. A. Serova1, N. A. Mazurkova1, A. A. Chernonosov2, A. Ya. Tikhonov3, and B. A. Selivanov3
Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 170, No. 8, pp. 173-177, August, 2020 Original article submitted January 23, 2020 We compared absolute bioavailability of the chemical substance of the anti-smallpox preparation NIOCH-14 and chemical compound ST-246 active against orthopoxviruses after oral administration to mice in doses of 10 and 50 μg/g and intravenous administration to mice in a dose of 2 μg/g body weight. The absolute bioavailability of NIOCH-14 is comparable with the absolute bioavailability of ST-246. Key Words: pharmacokinetics; bioavailability; anti-smallpox preparations; mice
On completion of the Global Smallpox Eradication Program and abolition of smallpox vaccination in 1980, the world has faced a dangerous situation where more than half population on the planet are not immune to orthopoxvirus infections. The problem of creating effective means for emergency prevention and treatment of infectious diseases caused by orthopoxviruses is still relevant because of the limited range of treatments for these diseases. In July 2018, the US Food and Drug Administration (FDA) registered the first drug for treating smallpox, Tecovirimat (TPOXX), created on the basis of the chemical compound ST246 (4-trifluoromethyl-N-(3,3a,4,4a,5,5a,6,6a-octahydro-1,3-dioxo-4,6-ethenocyclopropane[f]isoindol2(1H)-yl)-benzamide) [5,7,8]. In cooperation with the N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division of the Russian Aca 1 State Research Center of Virology and Biotechnology “Vector”, Fe deral Service for Surveillance on Consumer Rights Protection and Human Wellbeing, Koltsovo, Novosibirsk region, Russia; 2Institute of Chemical Biology and Fundamental Medicine, Siberian Division of the Russian Academy of Sciences, Novosibirsk, Russia; 3N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Division of Russian Academy of Sciences, Novosibirsk, Russia. Address for correspondence: [email protected]. O. Yu. Mazurkov
demy of Sciences, we obtained a new chemical compound NIOCH-14 (7-[N’-(4-trifluoromethylbenzoyl)hydrazinocarbonyl]-tricyclo[3.2.2.02,4]non-8-en-6-carboxylic acid), an analogue of ST-246 that has comparable activity against orthopoxviruses and was recommended as a substance for a domestic anti-smallpox drug [1,2,6]. The goal of the work was a comparative study of the absolute bioavailability of the substance of the anti-smallpox preparation NIOCH-14 and chemical compound ST-246 in mice.
MATERIALS AND METHODS The chemical compound NIOCH-14 synthesized at the N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry according to the developed methodology was used in the study [1,2]. Chemical compound ST246 (4-trifluoromethyl-N-(3,3a,4,4a,5,5a,6,6a-octahydro-1,3-dio
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