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Revealing the Regio...
Revealing the Regional Localization and Differential Lung Retention of Inhaled Compounds by Mass Spectrometry Imaging
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- Hamm, Gregory R. (författare)
- AstraZeneca, BioPharmaceut R&D, Pathol Sci, Clin Pharmacol & Safety Sci, Cambridge CB4 0WG, England
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- Bäckström, Erica (författare)
- AstraZeneca, BioPharmaceut R&D, Drug Metab & Pharmacokinet, Res & Early Dev,Resp Inflammat & Autoimmune, Gothenburg, Sweden
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- Brülls, Mikael (författare)
- AstraZeneca, BioPharmaceut R&D, Pharmaceut Sci, Early Prod Dev, Gothenburg, Sweden
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- Nilsson, Anna (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab
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- Strittmatter, Nicole (författare)
- AstraZeneca, BioPharmaceut R&D, Pathol Sci, Clin Pharmacol & Safety Sci, Cambridge CB4 0WG, England
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- Andrén, Per E. (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,Science for Life Laboratory, SciLifeLab
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- Grime, Ken (författare)
- AstraZeneca, BioPharmaceut R&D, Drug Metab & Pharmacokinet, Res & Early Dev,Resp Inflammat & Autoimmune, Gothenburg, Sweden
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- Fridén, Markus (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,AstraZeneca, BioPharmaceut R&D, Drug Metab & Pharmacokinet, Res & Early Dev,Resp Inflammat & Autoimmune, Gothenburg, Sweden
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- Goodwin, Richard J. A. (författare)
- AstraZeneca, BioPharmaceut R&D, Pathol Sci, Clin Pharmacol & Safety Sci, Cambridge CB4 0WG, England
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(creator_code:org_t)
- Mary Ann Liebert Inc, 2020
- 2020
- Engelska.
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Ingår i: Journal of Aerosol Medicine. - : Mary Ann Liebert Inc. - 1941-2711 .- 1941-2703. ; 33:1, s. 43-53
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Background: For the treatment of respiratory disease, inhaled drug delivery aims to provide direct access to pharmacological target sites while minimizing systemic exposure. Despite this long-held tenet of inhaled therapeutic advantage, there are limited data of regional drug localization in the lungs after inhalation. The aim of this study was to investigate the distribution and retention of different chemotypes typifying available inhaled drugs [slowly dissolving neutral fluticasone propionate (FP) and soluble bases salmeterol and salbutamol] using mass spectrometry imaging (MSI).Methods: Salmeterol, salbutamol, and FP were simultaneously delivered by inhaled nebulization to rats. In the same animals, salmeterol-d(3), salbutamol-d(3), and FP-d(3) were delivered by intravenous (IV) injection. Samples of lung tissue were obtained at 2- and 30-minute postdosing, and high-resolution MSI was used to study drug distribution and retention.Results: IV delivery resulted in homogeneous lung distribution for all molecules. In comparison, while inhalation also gave rise to drug presence in the entire lung, there were regional chemotype-dependent areas of higher abundance. At the 30-minute time point, inhaled salmeterol and salbutamol were preferentially retained in bronchiolar tissue, whereas FP was retained in all regions of the lungs.Conclusion: This study clearly demonstrates that inhaled small molecule chemotypes are differentially distributed in lung tissue after inhalation, and that high-resolution MSI can be applied to study these retention patterns.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Lungmedicin och allergi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Respiratory Medicine and Allergy (hsv//eng)
Nyckelord
- lung retention
- mass spectrometry imaging
- pharmacokinetics
- pulmonary distribution
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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