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Uncovering the regional localization of inhaled salmeterol retention in the lung
AstraZeneca, Resp Inflammat & Autoimmun IMED Biotech Unit, Drug Metab & Pharmacokinet, Gothenburg, Sweden.
AstraZeneca, Pathol Sci Drug Safety & Metab IMED Biotech Unit, Cambridge, England.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences. Uppsala University, Science for Life Laboratory, SciLifeLab.
AstraZeneca, Resp Inflammat & Autoimmun IMED Biotech Unit, Drug Metab & Pharmacokinet, Gothenburg, Sweden.
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2018 (English)In: Drug Delivery, ISSN 1071-7544, E-ISSN 1521-0464, Vol. 25, no 1, p. 838-845Article in journal (Refereed) Published
Abstract [en]

Treatment of respiratory disease with a drug delivered via inhalation is generally held as being beneficial as it provides direct access to the lung target site with a minimum systemic exposure. There is however only limited information of the regional localization of drug retention following inhalation. The aim of this study was to investigate the regional and histological localization of salmeterol retention in the lungs after inhalation and to compare it to systemic administration. Lung distribution of salmeterol delivered to rats via nebulization or intravenous (IV) injection was analyzed with high-resolution mass spectrometry imaging (MSI). Salmeterol was widely distributed in the entire section at 5 min after inhalation, by 15 min it was preferentially retained in bronchial tissue. Via a novel dual-isotope study, where salmeterol was delivered via inhalation and d(3)-salmeterol via IV to the same rat, could the effective gain in drug concentration associated with inhaled delivery relative to IV, expressed as a site-specific lung targeting factor, was 5-, 31-, and 45-fold for the alveolar region, bronchial sub-epithelium and epithelium, respectively. We anticipate that this MSI-based framework for quantifying regional and histological lung targeting by inhalation will accelerate discovery and development of local and more precise treatments of respiratory disease.

Place, publisher, year, edition, pages
Taylor & Francis Group, 2018. Vol. 25, no 1, p. 838-845
Keywords [en]
Pulmonary distribution, lung retention, mass spectrometry imaging, pharmacokinetics, inhalation
National Category
Respiratory Medicine and Allergy Pharmacology and Toxicology
Identifiers
URN: urn:nbn:se:uu:diva-354345DOI: 10.1080/10717544.2018.1455762ISI: 000428782700002PubMedID: 29587546OAI: oai:DiVA.org:uu-354345DiVA, id: diva2:1237130
Funder
AstraZenecaSwedish Research Council, 2014-6215Swedish Foundation for Strategic Research , RIF14-0078Available from: 2018-08-07 Created: 2018-08-07 Last updated: 2018-08-07Bibliographically approved

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