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Pharmocogenetic predictors of inhaled budesonide response in asthma
Author(s) -
Mackenzie Constance A,
Kim Richard B
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.667.1
Subject(s) - budesonide , pharmacogenetics , asthma , exhaled nitric oxide , medicine , cyp3a5 , formoterol , pharmacology , cyp3a4 , spirometry , genotype , chemistry , cytochrome p450 , biochemistry , metabolism , gene
There is considerable interindividual variability in response to inhaled corticosteroids for treatment of asthma. Although there is evidence that some of this variability is mediated by genetic factors, as of yet, there are no clear predictors of clinical response to inhaled steroids, particularly in relation to drug metabolism and transport processes. The goal of our study was to better understand the contribution of pharmacogenetic differences for patients with asthma whose treatment regimen includes budesonide, a widely prescribed inhaled steroid, known to be metabolized by CYP3A4 and transported by MDR1(ABCB1). We have enrolled 50 patients with confirmed asthma who were on a stable dose of inhaled budesonide alone (Pulmicort) or in combination with a long acting beta‐agonist formoterol (Symbicort). We will genotype for known polymorphisms in CYP3A4 (*22) and CYP3A5*3, as well as commonly occurring polymorphisms in MDR1. Importantly, we will also measure beta‐hydroxycholesterol/cholesterol ratio as an in vivo probe of CYP3A activity and measure budesonide plasma levels using highly sensitive liquid chromatography‐tandem mass spectrometry. Pharmacogenetic markers will be correlated with drug levels, clinical efficacy, pulmonary function, and exhaled nitric oxide as a marker of airway inflammation. Our findings will lead to better pharmacogenetic predictors of inhaled steroid therapy efficacy. Supported by Program of Experimental Medicine, Department of Medicine, Western University.