onr:"swepub:oai:DiVA.org:uu-13727"
Search: onr:"swepub:oai:DiVA.org:uu-13727" > An integrated model...
- 1 of 1
- Previous record
- Next record
- To hitlist
An integrated model for the effect of budesonide on ACTH and cortisol in healthy volunteers
-
- Lönnebo, Anna (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
-
- Grahnén, Anders (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
-
- Karlsson, Mats O. (author)
- Uppsala universitet,Institutionen för farmaceutisk biovetenskap
- (creator_code:org_t)
- Wiley, 2007
- 2007
- English.
- In: British Journal of Clinical Pharmacology. - : Wiley. - 0306-5251 .- 1365-2125. ; 64:2, s. 125-132
- Journal article (peer-reviewed)
Abstract
Subject headings
Close
- Aims: Budesonide, a glucocorticosteroid, is used as a first-line treatment for asthma. The aim of the study was to develop a PK/PD model for the effect of budesonide on ACTH and cortisol. Methods: The modelling data were generated by conducting a single-blind, randomized, placebo-controlled cross-over study. Ten healthy volunteers inhaled placebo (Placebo Turbohaler) and 1600 μg budesonide (Pulmicort Turbohaler), with a wash-out period of 7 days between treatments. Baseline concentrations of cortisol and ACTH were measured after placebo treatment and concentrations of cortisol, ACTH and budesonide were assessed after budesonide treatment. A one-compartment disposition model was used for budesonide disposition. Based on indirect response models, two types of models, distinguishing between production driven by a sum of cosine functions and production driven by surges, were used in parallel to describe the data. Results: The surge-based approach was the most appropriate, based on goodness-of-fit, objective function values and number of parameters. The surge-based model that integrated both ACTH and cortisol data was chosen as the final model. The estimated half-lives of endogenous ACTH and cortisol were 9 and 113 min, respectively. The budesonide and ACTH concentrations producing 50% of the maximal response (IC50 and A50) were 0.325 μg l-1 and 4.96 pmol l-1. Conclusions: The present PK/PD model of the effect of budesonide on ACTH and cortisol can serve as a tool for further understanding of the hypothalamic-pituitary-adrenal (HPA) axis and be useful in the development of drugs interacting with the axis.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Keyword
- ACTH
- Circadian variation
- Cortisol
- HPA axis
- Modelling
- Population pharmacokinetics-pharmacodynamics
- PHARMACY
- FARMACI
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
- British Journal of Clinical Pharmacology (Search for host publication in LIBRIS)
To the university's database
- 1 of 1
- Previous record
- Next record
- To hitlist
Find more in SwePub
- By the author/editor
- Lönnebo, Anna
- Grahnén, Anders
- Karlsson, Mats O ...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
- MEDICAL AND HEAL ...
- and Basic Medicine
- and Pharmaceutical S ...
- Articles in the publication
- British Journal ...
- By the university
- Uppsala University
Search outside SwePub
- Extend your search to:
- Google Book Search
- Google Scholar
Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.
- Copyright © LIBRIS - National Library Systems
- LIBRIS.kb.se
