ArticleThe Journal of pharmacology and experimental therapeutics2013
Metabolism of beclomethasone dipropionate by cytochrome P450 3A enzymes.
Article in The Journal of pharmacology and experimental therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 37 citations in OpenAlex.
- Eosinophil-derived interleukin-24 compromises epithelial integrity and aggravates airway remodeling in mouse models of allergic asthma.Nature communications · 2025Article
- The Cytochrome P450 2C8*3 Variant (rs11572080) Is Associated with Improved Asthma Symptom Control in Children and Altered Lipid Mediator Production and Inflammatory Response in Human Bronchial Epithelial Cells.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- Impact of CYP3A5 Polymorphisms on Pediatric Asthma Outcomes.International journal of molecular sciences · 2024Article
- Oral beclomethasone dipropionate as an add-on therapy and response prediction in Korean patients with ulcerative colitis.The Korean journal of internal medicine · 2022Article
- Neonatal cytochrome P450 CYP3A7: A comprehensive review of its role in development, disease, and xenobiotic metabolism.Archives of biochemistry and biophysics · 2019Review
- Early Diagnosis of Latent Tuberculosis Reactivation due to Drug Interaction between Cobicistat and Intranasal Fluticasone.Case reports in infectious diseases · 2019Article
- Discovery of super soft-drug modulators of sphingosine-1-phosphate receptor 1.Bioorganic & medicinal chemistry letters · 2018Article
- Long-Term Fluticasone Propionate/Formoterol Fumarate Combination Therapy Is Associated with a Low Incidence of Severe Asthma Exacerbations.Journal of aerosol medicine and pulmonary drug delivery · 2016Article
- Effect of CYP3A5*3 on asthma control among children treated with inhaled beclomethasone.The Journal of allergy and clinical immunology · 2015Article
- Article
- Regulation of CYP3A genes by glucocorticoids in human lung cells.F1000Research · 2013Article
- Why small particle fixed dose triple therapy? An excursus from COPD pathology to pharmacological treatment evolution.Therapeutic advances in respiratory diseaseArticle
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Inhaled glucocorticoids, such as beclomethasone dipropionate (BDP), are the mainstay treatment of asthma. However, ≈ 30% of patients exhibit little to no benefit from treatment. It has been postulated that glucocorticoid resistance, or insensitivity, is attributable to individual differences in glucocorticoid receptor-mediated processes. It is possible that variations in cytochrome P450 3A enzyme-mediated metabolism of BDP may contribute to this phenomenon. This hypothesis was explored by evaluating the contributions of CYP3A4, 3A5, 3A7, and esterase enzymes in the metabolism of BDP in vitro and relating metabolism to changes in CYP3A enzyme mRNA expression via the glucocorticoid receptor in lung and liver cells. CYP3A4 and CYP3A5 metabolized BDP via hydroxylation ([M4] and [M6]) and dehydrogenation ([M5]) at similar rates; CYP3A7 did not metabolize BDP. A new metabolite [M6], formed by the combined action of esterases and CYP3A4 hydroxylation, was also characterized. To validate the results observed using microsomes and recombinant enzymes, studies were also conducted using A549 lung and DPX2 liver cells. Both liver and lung cells produced esterase-dependent metabolites [M1-M3], with [M1] correlating with CYP3A5 mRNA induction in A549 cells. Liver cells produced both hydroxylated and dehydrogenated metabolites [M4, M5, and M6], but lung cells produced only the dehydrogenated metabolite [M5]. These studies show that CYP3A4 and CYP3A5 metabolize BDP to inactive metabolites and suggest that differences in the expression or function of these enzymes in the lung and/or liver could influence BDP disposition in humans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.