title: 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.
authors.affiliation: WHO Collaborating Centre for Reference and Research on Influenza, VIDRL, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia; School of Applied Sciences and Engineering, Monash University, Churchill, Victoria 3842, Australia. Electronic address: jacquipanozzo@gmail.com.
authors.forename: Jacqueline
authors.initials: J
authors.lastname: Panozzo
authors.affiliation: WHO Collaborating Centre for Reference and Research on Influenza, VIDRL, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia; School of Applied and Biomedical Sciences, Federation University, Churchill, Victoria 3842, Australia. Electronic address: DingThomas.Oh@influenzacentre.org.
authors.forename: Ding Yuan
authors.initials: DY
authors.lastname: Oh
authors.affiliation: Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia. Electronic address: Kenneth.Margo@monash.edu.
authors.forename: Kenneth
authors.initials: K
authors.lastname: Margo
authors.affiliation: Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade, Parkville, Victoria 3052, Australia. Electronic address: David.Morton@monash.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Morton
authors.affiliation: School of Applied and Biomedical Sciences, Federation University, Churchill, Victoria 3842, Australia. Electronic address: david.piedrafita@federation.edu.au.
authors.forename: David
authors.initials: D
authors.lastname: Piedrafita
authors.affiliation: School of Applied and Biomedical Sciences, Federation University, Churchill, Victoria 3842, Australia. Electronic address: jennifer.mosse@federation.edu.au.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Mosse
authors.affiliation: WHO Collaborating Centre for Reference and Research on Influenza, VIDRL, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria 3000, Australia; Melbourne School of Population and Global Health, University of Melbourne, Parkville, Victoria 3010, Australia. Electronic address: Aeron.hurt@influenzacentre.org.
authors.forename: Aeron C
authors.initials: AC
authors.lastname: Hurt
mesh_terms: D000280:Administration, Inhalation; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000008:administration & dosage*; D005289:Ferrets; D006146:Guanidines; D009976:Orthomyxoviridae Infections / Q000188:drug therapy*; D010919:Placebos / Q000008:administration & dosage; D011208:Powders / Q000008:administration & dosage*; D011714:Pyrans; D012794:Sialic Acids; D053243:Zanamivir / Q000008:administration & dosage / Q000031:analogs & derivatives*
chemical_list: D000998:Antiviral Agents; D004337:Drug Carriers; D006146:Guanidines; D010919:Placebos; D011208:Powders; D011714:Pyrans; D012794:Sialic Acids; C546918:laninamivir; D053243:Zanamivir
keywords: Antiviral; Ferrets; Influenza; Laninamivir; Neuraminidase inhibitor; Powder delivery