Skip to main content

Main menu

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • ERS Guidelines
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Open access
    • COVID-19 submission information
    • Peer reviewer login
  • Alerts
  • Subscriptions
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

User menu

  • Log in
  • Subscribe
  • Contact Us
  • My Cart

Search

  • Advanced search
  • ERS Publications
    • European Respiratory Journal
    • ERJ Open Research
    • European Respiratory Review
    • Breathe
    • ERS Books
    • ERS publications home

Login

European Respiratory Society

Advanced Search

  • Home
  • Current issue
  • ERJ Early View
  • Past issues
  • ERS Guidelines
  • Authors/reviewers
    • Instructions for authors
    • Submit a manuscript
    • Open access
    • COVID-19 submission information
    • Peer reviewer login
  • Alerts
  • Subscriptions

Prediction of human lung PK for AZD7624, an inhaled P38 inhibitor for the treatment of COPD

Sara Asimus, Mats Någård, Rikard Pehrson, Tove Hegelund, Paul Jansson, Naimish Patel
European Respiratory Journal 2015 46: PA3950; DOI: 10.1183/13993003.congress-2015.PA3950
Sara Asimus
3Quantitative Clinical Pharmacology, AstraZeneca R&D, Mölndal, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mats Någård
1Quantitative Clinical Pharmacology, AstraZeneca R&D, Gaithersburg, MD United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rikard Pehrson
2RIA iMed DMPK, AstraZeneca R&D, Mölndal, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Tove Hegelund
2RIA iMed DMPK, AstraZeneca R&D, Mölndal, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Paul Jansson
4iMed Respiratory/Inflammation, AstraZeneca R&D, Mölndal, Sweden
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Naimish Patel
5Early Clinical Development, AstraZeneca R&D, Waltham, MA United States
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
Loading

Abstract

Inhibition of p38 mitogen-activated protein kinases has been suggested as novel treatment for COPD. However, since p38 has high expression in tissues other than lung, local delivery may be crucial for an effective treatment while reducing potential unwanted side effects driven by systemic exposure. AZD7624 is a novel P38 inhibitor designed for inhaled administration for COPD. Here we examined the lung and plasma pharmacokinetic (PK) profile of AZD7624 in a rat inhalation model to predict human PK profile, which was validated in a human single ascending dose study.

Rats were administrated a single dose of AZD7624 either through dry powder inhalation or intravenously. Lung tissue and plasma samples were taken up to 80 hours post dose for PK determination. AZD7624 (29, 101, 336, 631, and 1177 µg single lung deposited dose) was administrated by inhalation to healthy volunteers and plasma samples were takenfor PK determination.

In the rat a long terminal half life in the lung of approximately 60 hours was observed. The ratio between lung and plasma concentration following inhalation was ∼500-1000 times during 24h while IV administration resulted in ∼10 times lower lung-plasma ratio.

The human plasma PK parameters were comparable across all doses, and characterized by a rapid absorption followed by a fast distribution phase and a long terminal half-life (64 - 72 h). The human plasma PK was in good agreement with the prediction based on the rat PK, and supports the prediction of a high lung concentration in man. Hence, AZD7624 appears to have promising PK properties for inhaled treatment of COPD.

  • Animal models
  • Anti-inflammatory
  • Copyright ©ERS 2015
Previous
Back to top
Vol 46 Issue suppl 59 Table of Contents
  • Table of Contents
  • Index by author
Email

Thank you for your interest in spreading the word on European Respiratory Society .

NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

Enter multiple addresses on separate lines or separate them with commas.
Prediction of human lung PK for AZD7624, an inhaled P38 inhibitor for the treatment of COPD
(Your Name) has sent you a message from European Respiratory Society
(Your Name) thought you would like to see the European Respiratory Society web site.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Prediction of human lung PK for AZD7624, an inhaled P38 inhibitor for the treatment of COPD
Sara Asimus, Mats Någård, Rikard Pehrson, Tove Hegelund, Paul Jansson, Naimish Patel
European Respiratory Journal Sep 2015, 46 (suppl 59) PA3950; DOI: 10.1183/13993003.congress-2015.PA3950

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Prediction of human lung PK for AZD7624, an inhaled P38 inhibitor for the treatment of COPD
Sara Asimus, Mats Någård, Rikard Pehrson, Tove Hegelund, Paul Jansson, Naimish Patel
European Respiratory Journal Sep 2015, 46 (suppl 59) PA3950; DOI: 10.1183/13993003.congress-2015.PA3950
Reddit logo Technorati logo Twitter logo Connotea logo Facebook logo Mendeley logo

Jump To

  • Article
  • Info & Metrics
  • Tweet Widget
  • Facebook Like
  • Google Plus One

More in this TOC Section

  • Direct activation of sensory afferents by diesel exhaust particles can trigger respiratory symptoms
  • Roflumilast but not dexamethasone or fluticasone reduces neutrophilic airway inflammation and hyperreactivity in a murine influenza-induced asthma exacerbation model
  • Dysphonia in asthmatic women using inhaled corticosteroids: It is not only a laryngeal inflammation
Show more 5.1 Airway Pharmacology and Treatment

Related Articles

Navigate

  • Home
  • Current issue
  • Archive

About the ERJ

  • Journal information
  • Editorial board
  • Press
  • Permissions and reprints
  • Advertising

The European Respiratory Society

  • Society home
  • myERS
  • Privacy policy
  • Accessibility

ERS publications

  • European Respiratory Journal
  • ERJ Open Research
  • European Respiratory Review
  • Breathe
  • ERS books online
  • ERS Bookshop

Help

  • Feedback

For authors

  • Instructions for authors
  • Publication ethics and malpractice
  • Submit a manuscript

For readers

  • Alerts
  • Subjects
  • Podcasts
  • RSS

Subscriptions

  • Accessing the ERS publications

Contact us

European Respiratory Society
442 Glossop Road
Sheffield S10 2PX
United Kingdom
Tel: +44 114 2672860
Email: journals@ersnet.org

ISSN

Print ISSN:  0903-1936
Online ISSN: 1399-3003

Copyright © 2023 by the European Respiratory Society