Advanced

Gene expression analysis of membrane transporters and drug-metabolizing enzymes in the lung of healthy and COPD subjects.

Berg, Tove; Hegelund Myrbäck, Tove; Olsson, Marita LU ; Seidegård, Janeric; Werkström, Viktoria LU ; Zhou, Xiao-Hong; Grunewald, Johan; Gustavsson, Lena LU and Nord, Magnus (2014) In Pharmacology research & perspectives 2(4). p.00054-00054
Abstract
This study describes for the first time the expression levels of genes encoding membrane transporters and drug-metabolizing enzymes in the lungs of ex-smoking patients with chronic obstructive pulmonary disease (COPD). Membrane transporters and drug-metabolizing enzymes are key determinants of drug uptake, metabolism, and elimination for systemically administered as well as inhaled drugs, with consequent influence on clinical efficacy and patient safety. In this study, while no difference in gene expression was found between healthy and COPD subjects, we identified a significant regional difference in mRNA expression of both membrane transporters and drug-metabolizing enzymes between central and peripheral tissue in both healthy and COPD... (More)
This study describes for the first time the expression levels of genes encoding membrane transporters and drug-metabolizing enzymes in the lungs of ex-smoking patients with chronic obstructive pulmonary disease (COPD). Membrane transporters and drug-metabolizing enzymes are key determinants of drug uptake, metabolism, and elimination for systemically administered as well as inhaled drugs, with consequent influence on clinical efficacy and patient safety. In this study, while no difference in gene expression was found between healthy and COPD subjects, we identified a significant regional difference in mRNA expression of both membrane transporters and drug-metabolizing enzymes between central and peripheral tissue in both healthy and COPD subjects. The majority of the differentially expressed genes were higher expressed in the central airways such as the transporters SLC2A1 (GLUT1), SLC28A3 (CNT3), and SLC22A4 (OCTN1) and the drug-metabolizing enzymes GSTZ1, GSTO2, and CYP2F1. Together, this increased knowledge of local pharmacokinetics in diseased and normal lung may improve modeling of clinical outcomes of new chemical entities intended for inhalation therapy delivered to COPD patients. In addition, based on the similarities between COPD and healthy subjects regarding gene expression of membrane transporters and drug-metabolizing enzymes, our results suggest that clinical pharmacological studies in healthy volunteers could be a valid model of COPD patients regarding drug disposition of inhaled drugs in terms of drug metabolism and drug transporters. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Pharmacology research & perspectives
volume
2
issue
4
pages
00054 - 00054
publisher
John Wiley & Sons
external identifiers
  • pmid:25505599
ISSN
2052-1707
DOI
10.1002/prp2.54
language
English
LU publication?
yes
id
79812e28-c70e-4ffc-ad99-e20c10964b3b (old id 4908263)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/25505599?dopt=Abstract
date added to LUP
2015-01-08 15:30:16
date last changed
2016-09-20 04:05:41
@article{79812e28-c70e-4ffc-ad99-e20c10964b3b,
  abstract     = {This study describes for the first time the expression levels of genes encoding membrane transporters and drug-metabolizing enzymes in the lungs of ex-smoking patients with chronic obstructive pulmonary disease (COPD). Membrane transporters and drug-metabolizing enzymes are key determinants of drug uptake, metabolism, and elimination for systemically administered as well as inhaled drugs, with consequent influence on clinical efficacy and patient safety. In this study, while no difference in gene expression was found between healthy and COPD subjects, we identified a significant regional difference in mRNA expression of both membrane transporters and drug-metabolizing enzymes between central and peripheral tissue in both healthy and COPD subjects. The majority of the differentially expressed genes were higher expressed in the central airways such as the transporters SLC2A1 (GLUT1), SLC28A3 (CNT3), and SLC22A4 (OCTN1) and the drug-metabolizing enzymes GSTZ1, GSTO2, and CYP2F1. Together, this increased knowledge of local pharmacokinetics in diseased and normal lung may improve modeling of clinical outcomes of new chemical entities intended for inhalation therapy delivered to COPD patients. In addition, based on the similarities between COPD and healthy subjects regarding gene expression of membrane transporters and drug-metabolizing enzymes, our results suggest that clinical pharmacological studies in healthy volunteers could be a valid model of COPD patients regarding drug disposition of inhaled drugs in terms of drug metabolism and drug transporters.},
  author       = {Berg, Tove and Hegelund Myrbäck, Tove and Olsson, Marita and Seidegård, Janeric and Werkström, Viktoria and Zhou, Xiao-Hong and Grunewald, Johan and Gustavsson, Lena and Nord, Magnus},
  issn         = {2052-1707},
  language     = {eng},
  number       = {4},
  pages        = {00054--00054},
  publisher    = {John Wiley & Sons},
  series       = {Pharmacology research & perspectives},
  title        = {Gene expression analysis of membrane transporters and drug-metabolizing enzymes in the lung of healthy and COPD subjects.},
  url          = {http://dx.doi.org/10.1002/prp2.54},
  volume       = {2},
  year         = {2014},
}