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

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

Журнал

Journal of Pharmaceutical Sciences
ISSN: 0022-3549 , E-ISSN: 1520-6017

Вых. Данные

Год: 2021, Том: 110, Номер: 3, Страницы: 1316-1322 Страниц : 7 DOI: 10.1016/j.xphs.2020.11.016

Ключевые слова

Antiviral drug; Bioavailability; Drug aerosol; Elimination rate; Pharmacokinetics; Pulmonary drug delivery; Triazavirin

Авторы

Valiulin Sergey V. ¹ , Onischuk Andrey A. ¹ , Dubtsov Sergey N. ¹ , Baklanov Anatoly M. ¹ , An'kov Sergey V. ² , Plokhotnichenko Maria E. ¹ , Tolstikova Tatyana G. ² , Dultseva Galina G. ¹ , Rusinov Vladimir L. ³ , Charushin Valery N. ³ , Fomin Vasily M. ⁴

Организации

1	Voevodsky Institute of Chemical Kinetics and Combustion, SB RAS, Novosibirsk, 630090, Russian Federation
2	Vorozhtsov Institute of Organic Chemistry, SB RAS, Novosibirsk, 630090, Russian Federation
3	Postovskii Institute of Organic Synthesis, UrB RAS, Yekaterinburg, 620137, Russian Federation
4	Khristianovich Institute of Theoretical and Applied Mechanics, SB RAS, Novosibirsk, 630090, Russian Federation

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®

Valiulin S.V. , Onischuk A.A. , Dubtsov S.N. , Baklanov A.M. , An'kov S.V. , Plokhotnichenko M.E. , Tolstikova T.G. , Dultseva G.G. , Rusinov V.L. , Charushin V.N. , Fomin V.M.
Aerosol Inhalation Delivery of Triazavirin in Mice: Outlooks for Advanced Therapy Against Novel Viral Infections

Journal of Pharmaceutical Sciences. 2021. V.110. N3. P.1316-1322. DOI: 10.1016/j.xphs.2020.11.016 WOS Scopus

Полный текст от издателя

Опубликована в печати:

1 нояб. 2020 г.

Web of science	WOS:000629663900037
Scopus	2-s2.0-85097469435
OpenAlex	W3110475791