Статья

Aerosol Inhalation Delivery of Triazavirin in Mice: Outlooks for Advanced Therapy Against Novel Viral Infections

S. Valiulin, A. Onischuk, S. Dubtsov, A. Baklanov, S. An'kov, M. Plokhotnichenko, T. Tolstikova, G. Dultseva, V. Rusinov, V. Charushin, V. Fomin,
2021

Under pandemic-caused emergency, evaluation of the potential of existing antiviral drugs for the treatment of COVID-19 is relevant. Triazavirin, an antiviral drug developed in Russia for per-oral administration, is involved in clinical trials against SARS-CoV-2 coronavirus. This virus has affinity to epithelial cells in respiratory tract, so drug delivery directly in lungs may enhance therapeutic effect and reduce side effects for stomach, liver, kidneys. We elaborated ultrasonic method of triazavirin aerosol generation and investigated the inhalation delivery of this drug in mice. Mean particle size and number concentration of aerosol used in inhalation experiments are 560 nm and 4 × 105 cm−3, respectively. Aerosol mass concentration is 1.6 × 10−4 mg/cm3. Inhalation for 20 min in a nose-only chamber resulted in 2 mg/kg body delivered dose and 2.6 μg/mL triazavirin concentration in blood plasma. Elimination rate constant determined in aerosol administration experiments was ke = 0.077 min−1, which agrees with the value measured after intravenous delivery, but per-oral administration resulted in considerably lower apparent elimination rate constant of pseudo-first order, probably due to non-linear dependence of absorption rate on triazavirin concentration in gastrointestinal tract. The bioavailability of triazavirin aerosol is found to be 85%, which is about four times higher than for per-oral administration. © 2020 American Pharmacists Association®

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  • 1. Version of Record от 2021-04-27

Метаданные

Об авторах
  • S. Valiulin
    Voevodsky Institute of Chemical Kinetics and Combustion, SB RAS, Novosibirsk, 630090, Russian Federation
  • A. Onischuk
    Vorozhtsov Institute of Organic Chemistry, SB RAS, Novosibirsk, 630090, Russian Federation
  • S. Dubtsov
    Postovskii Institute of Organic Synthesis, UrB RAS, Yekaterinburg, 620137, Russian Federation
  • A. Baklanov
    Khristianovich Institute of Theoretical and Applied Mechanics, SB RAS, Novosibirsk, 630090, Russian Federation
  • S. An'kov
  • M. Plokhotnichenko
  • T. Tolstikova
  • G. Dultseva
  • V. Rusinov
  • V. Charushin
  • V. Fomin
Название журнала
  • Journal of Pharmaceutical Sciences
Том
  • 110
Выпуск
  • 3
Страницы
  • 1316-1322
Ключевые слова
  • riamilovir; animal experiment; Article; concentration (parameter); controlled study; drug absorption; drug bioavailability; drug blood level; drug efficacy; elimination rate constant; male; mouse; nonhuman; particle size; Severe acute respiratory syndrome coronavirus 2; virus infection
Издатель
  • Elsevier B.V.
Тип документа
  • journal article
Тип лицензии Creative Commons
  • CC
Правовой статус документа
  • Свободная лицензия
Источник
  • scopus