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Lung Retention by L...
Lung Retention by Lysosomal Trapping of Inhaled Drugs Can Be Predicted In Vitro With Lung Slices
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- Bäckström, Erica (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,AstraZeneca R&D Gothenburg, Resp Inflammat & Autoimmun Innovat Med, S-43183 Molndal, Sweden.
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- Boger, Elin (författare)
- AstraZeneca R&D Gothenburg, Resp Inflammat & Autoimmun Innovat Med, S-43183 Molndal, Sweden.;Univ Warwick, Sch Engn, Coventry CV4 7AL, W Midlands, England.
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- Lundqvist, Anders (författare)
- AstraZeneca R&D Gothenburg, Resp Inflammat & Autoimmun Innovat Med, S-43183 Molndal, Sweden.
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- Hammarlund-Udenaes, Margareta (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
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- Fridén, Markus (författare)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap,AstraZeneca R&D Gothenburg, Resp Inflammat & Autoimmun Innovat Med, S-43183 Molndal, Sweden.
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(creator_code:org_t)
- Elsevier BV, 2016
- 2016
- Engelska.
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Ingår i: Journal of Pharmaceutical Sciences. - : Elsevier BV. - 0022-3549 .- 1520-6017. ; 105:11, s. 3432-3439
- 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
- Modulating and optimizing the local pharmacokinetics of inhaled drugs by chemical design or formulation is challenged by the lack of predictive in vitro systems and in vivo techniques providing a detailed description of drug location in the lung. The present study investigated whether a new experimental setup of freshly prepared agarose-filled lung slices can be used to estimate lung retention in vitro, by comparing with in vivo lung retention after intratracheal instillation. Slices preloaded with inhaled beta-adrenergic compounds (salbutamol, formoterol, salmeterol, indacaterol or AZD3199) were incubated in a large volume of buffer (w/wo monensin to assess the role of lysosomal trapping), and the amount remaining in slices at different time points was determined with liquid chromatography-tandem mass spectrometry. The in vitro lung retention closely matched the in vivo lung retention (half-lives within 3-fold for 4/5 compounds), and monensin shortened the half-lives for all compounds. The results suggest that freshly prepared rat lungs slices can be used to predict lung retention and that slow kinetics of lysosomal trapping is a key mechanism by which retention in the lung and the effect duration of inhaled beta-adrenergic bronchodilators are prolonged.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- pharmacokinetics
- pulmonary drug delivery
- tissue partition
- distribution
- pulmonary
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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