Document Detail

A pharmacokinetic simulation tool for inhaled corticosteroids.
MedLine Citation:
PMID:  23139018     Owner:  NLM     Status:  MEDLINE    
The pharmacokinetic (PK) behavior of inhaled drugs is more complicated than that of other forms of administration. In particular, the effects of certain physiological (mucociliary clearance and differences in membrane properties in central and peripheral (C/P) areas of the lung), formulation (as it relates to drug deposition and particle dissolution rate), and patient-related factors (lung function; effects on C/P deposition ratio) affect the systemic PKs of inhaled drugs. The objectives of this project were (1) to describe a compartmental model that adequately describes the fate of inhaled corticosteroids (ICS) after administration while incorporating variability between and within subjects and (2) based upon the model, to provide a freely available tool for simulation of PK trials after ICS administration. This compartment model allows for mucociliary removal of undissolved particles from the lung, distinguishes between central and peripheral regions of the lung, and models drug entering the systemic circulation via the lung and the gastrointestinal tract. The PK simulation tool is provided as an extension package to the statistical software R ('ICSpkTS'). It allows simulation of PK trials for hypothetical ICS and of four commercially available ICS (budesonide, flunisolide, fluticasone propionate, and triamcinolone acetonide) in a parallel study design. Simulated PK data and parameters agreed well with literature data for all four ICS. The ICSpkTS package is especially suitable to explore the effect of changes in model parameters on PK behavior and can be easily adjusted for other inhaled drugs.
Benjamin Weber; Guenther Hochhaus
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Publication Detail:
Type:  Journal Article     Date:  2012-11-10
Journal Detail:
Title:  The AAPS journal     Volume:  15     ISSN:  1550-7416     ISO Abbreviation:  AAPS J     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-03     Completed Date:  2013-08-02     Revised Date:  2013-11-14    
Medline Journal Info:
Nlm Unique ID:  101223209     Medline TA:  AAPS J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  159-71     Citation Subset:  IM    
Department of Pharmaceutics, College of Pharmacy, Center of Pharmacometrics and Systems Pharmacology, University of Florida, 1600 SW Archer Road, P3-33, Gainesville, FL 32610, USA.
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MeSH Terms
Administration, Inhalation
Adrenal Cortex Hormones / administration & dosage,  pharmacokinetics*
Clinical Trials as Topic
Models, Biological
Reg. No./Substance:
0/Adrenal Cortex Hormones

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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