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Evaluation of a dry powder delivery system for laninamivir in a ferret model of influenza infection.

Abstract
Laninamivir is a long-acting antiviral requiring only a single dose for the treatment of influenza infection, making it an attractive alternative to existing neuraminidase inhibitors that require multiple doses over many days. Like zanamivir, laninamivir is administered to patients by inhalation of dry powder. To date, studies investigating the effectiveness of laninamivir or zanamivir in a ferret model of influenza infection have administered the drug in a solubilised form. To better mimic the delivery action of laninamivir in humans, we assessed the applicability of a Dry Powder Insufflator™ (DPI) as a delivery method for laninamivir octanoate (LO) in ferrets to determine the effectiveness of this drug in reducing influenza A and B virus infections. In vitro characterisation of the DPI showed that both the small particle sized LO (0.7-6.0μm diameter) and the large particle sized lactose carrier (20-100μm diameter) were effectively discharged. However, LO delivered to ferrets via the DPI prior to infection with either A(H1N1)pdm09 or B viruses had a limited effect on nasal inflammation, clinical symptoms and viral shedding compared to placebo. Our preliminary findings indicate the feasibility of administering powder drugs into ferrets, but a better understanding of the pharmacokinetics and pharmacodynamics of LO in ferrets following delivery by the DPI is warranted prior to further studies.
AuthorsJacqueline Panozzo, Ding Yuan Oh, Kenneth Margo, David A Morton, David Piedrafita, Jennifer Mosse, Aeron C Hurt
JournalAntiviral research (Antiviral Res) Vol. 120 Pg. 66-71 (Aug 2015) ISSN: 1872-9096 [Electronic] Netherlands
PMID26022199 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier B.V. All rights reserved.
Chemical References
  • Antiviral Agents
  • Drug Carriers
  • Guanidines
  • Placebos
  • Powders
  • Pyrans
  • Sialic Acids
  • laninamivir
  • Zanamivir
Topics
  • Administration, Inhalation
  • Animals
  • Antiviral Agents (administration & dosage)
  • Disease Models, Animal
  • Drug Carriers (administration & dosage)
  • Ferrets
  • Guanidines
  • Orthomyxoviridae Infections (drug therapy)
  • Placebos (administration & dosage)
  • Powders (administration & dosage)
  • Pyrans
  • Sialic Acids
  • Zanamivir (administration & dosage, analogs & derivatives)

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