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Aerosol Inhalation Delivery of Triazavirin in Mice: Outlooks for Advanced Therapy Against Novel Viral Infections.
- Source :
-
Journal of pharmaceutical sciences [J Pharm Sci] 2021 Mar; Vol. 110 (3), pp. 1316-1322. Date of Electronic Publication: 2020 Nov 26. - Publication Year :
- 2021
-
Abstract
- 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 × 10 <superscript>5</superscript>  cm <superscript>-3</superscript> , respectively. Aerosol mass concentration is 1.6 × 10 <superscript>-4</superscript>  mg/cm <superscript>3</superscript> . 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 k <subscript>e</subscript>  = 0.077 min <superscript>-1</superscript> , 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.<br /> (Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Administration, Inhalation
Administration, Oral
Aerosols pharmacokinetics
Animals
Antiviral Agents blood
Antiviral Agents pharmacokinetics
Azoles blood
Azoles pharmacokinetics
Biological Availability
Drug Delivery Systems instrumentation
Drug Elimination Routes
Equipment Design
Humans
Male
Mice
Triazines blood
Triazines pharmacokinetics
Triazoles
COVID-19 Drug Treatment
Aerosols administration & dosage
Antiviral Agents administration & dosage
Azoles administration & dosage
Nebulizers and Vaporizers
Triazines administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1520-6017
- Volume :
- 110
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of pharmaceutical sciences
- Publication Type :
- Academic Journal
- Accession number :
- 33249050
- Full Text :
- https://doi.org/10.1016/j.xphs.2020.11.016