Comparison of Oral, Intranasal and Aerosol Administration of Amiodarone in Rats as a Model of Pulmonary Phospholipidosis.

amiodarone di-22:6 bis-monoacylglycerol foamy alveolar macrophages high content analysis mass spectrometry imaging phospholipidosis

Journal

Pharmaceutics
ISSN: 1999-4923
Titre abrégé: Pharmaceutics
Pays: Switzerland
ID NLM: 101534003

Informations de publication

Date de publication:
17 Jul 2019
Historique:
received: 31 05 2019
revised: 10 07 2019
accepted: 11 07 2019
entrez: 20 7 2019
pubmed: 20 7 2019
medline: 20 7 2019
Statut: epublish

Résumé

'Foamy' alveolar macrophages (FAM) observed in nonclinical toxicology studies during inhaled drug development may indicate drug-induced phospholipidosis, but can also derive from adaptive non-adverse mechanisms. Orally administered amiodarone is currently used as a model of pulmonary phospholipidosis and it was hypothesized that aerosol administration would produce phospholipidosis-induced FAM that could be characterized and used in comparative inhalation toxicology. Han-Wistar rats were given amiodarone via (1) intranasal administration (6.25 mg/kg) on two days, (2) aerosol administration (3 mg/kg) on two days, (3) aerosol administration (10 mg/kg) followed by three days of 30 mg/kg or (4) oral administration (100 mg/kg) for 7 days. Alveolar macrophages in bronchoalveolar lavage were evaluated by differential cell counting and high content fluorescence imaging. Histopathology and mass-spectrometry imaging (MSI) were performed on lung slices. The higher dose aerosolised amiodarone caused transient pulmonary inflammation (

Identifiants

DOI: 10.3390/pharmaceutics11070345 PMID: 31319538 PMC: PMC6680908
pubmed: 31319538
pii: pharmaceutics11070345
doi: 10.3390/pharmaceutics11070345
pmc: PMC6680908
pii:
doi:

Types de publication

Journal Article

Langues

eng

Subventions

Organisme : National Centre for the Replacement, Refinement and Reduction of Animals in Research
ID : NC/L001683/1
Pays : United Kingdom
Organisme : National Centre for the Replacement Refinement and Reduction of Animals in Research
ID : NC/L001683/1
Organisme : National Centre for the Replacement, Refinement and Reduction of Animals in Research
ID : NC/C013203/1
Pays : United Kingdom
Organisme : National Centre for the Replacement, Refinement and Reduction of Animals in Research
ID : NC/C013109/1
Pays : United Kingdom
Organisme : National Centre for the Replacement Refinement and Reduction of Animals in Research
ID : NC/CO13203/1

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Auteurs

Aateka Patel (A)

Sackler Institute of Pulmonary Pharmacology, Faculty of Life Sciences & Medicine, Franklin-Wilkins Building, King's College London, 150 Stamford Street, London SE1 9NH, UK.
Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, King's College London, 150 Stamford Street, London SE1 9NH, UK.
ORCID: 0000-0002-4172-0827

Ewelina Hoffman (E)

Centre for Topical Drug Delivery and Toxicology, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, Herts AL10 9AB, UK.
Department of Pharmaceutical Biochemistry and Molecular Diagnostics, Pharmacy Faculty, Medical University of Lodz, 90-151 Lodz, Poland.
ORCID: 0000-0002-7998-924X

Doug Ball (D)

Allergic Inflammation Discovery Performance Unit, GlaxoSmithKline, Gunnelswood Road, Stevenage, Herts SG1 2NY, UK.

Jan Klapwijk (J)

Translational Medicine and Comparative Pathobiology, GlaxoSmithKline, Park Road, Ware, Hertfordshire SG12 0DP, UK.

Rory T Steven (RT)

National Physical Laboratory, Teddington, London TW11 0LW, UK.

Alex Dexter (A)

National Physical Laboratory, Teddington, London TW11 0LW, UK.

Josephine Bunch (J)

National Physical Laboratory, Teddington, London TW11 0LW, UK.

Daniel Baker (D)

Centre for Topical Drug Delivery and Toxicology, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, Herts AL10 9AB, UK.

Darragh Murnane (D)

Centre for Topical Drug Delivery and Toxicology, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, Herts AL10 9AB, UK.

Victoria Hutter (V)

Centre for Topical Drug Delivery and Toxicology, School of Life and Medical Sciences, University of Hertfordshire, Hatfield, Herts AL10 9AB, UK.

Clive Page (C)

Sackler Institute of Pulmonary Pharmacology, Faculty of Life Sciences & Medicine, Franklin-Wilkins Building, King's College London, 150 Stamford Street, London SE1 9NH, UK.

Lea Ann Dailey (LA)

Institute of Pharmaceutical Technology and Biopharmacy, Martin Luther University Halle-Wittenberg, Wolfgang-Langenbeck-Str. 4, 06108 Halle (Saale), Germany. lea.dailey@pharmazie.uni-halle.de.

Ben Forbes (B)

Institute of Pharmaceutical Science, King's College London, Franklin-Wilkins Building, King's College London, 150 Stamford Street, London SE1 9NH, UK.
ORCID: 0000-0001-8193-6107

Classifications MeSH