ArticleBritish journal of clinical pharmacology2019
Activity and mRNA expression levels of selected cytochromes P450 in various sections of the human small intestine.
Article in British journal of clinical pharmacology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 28 citations in OpenAlex.
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- Prodrugs in Oncology: Bioactivation and Impact on Therapeutic Efficacy and Toxicity.International journal of molecular sciences · 2025Review
- Isoform-level expression of the constitutive androstane receptor (CAR or NR1I3) transcription factor better predicts the mRNA expression of the cytochrome P450s in human liver samples.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Clinical Effects of Exercise Rehabilitation Combined with Repaglinide in the Treatment of Diabetes.Disease markers · 2022Article
- Determination of CYP450 Expression Levels in the Human Small Intestine by Mass Spectrometry-Based Targeted Proteomics.International journal of molecular sciences · 2021Article
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- Contribution of CYP2D6 Functional Activity to Oxycodone Efficacy in Pain Management: Genetic Polymorphisms, Phenoconversion, and Tissue-Selective Metabolism.Pharmaceutics · 2021Review
- Gene Expression and Protein Abundance of Hepatic Drug Metabolizing Enzymes in Liver Pathology.Pharmaceutics · 2021Article
- Drug-Drug Interactions Involving Intestinal and Hepatic CYP1A Enzymes.Pharmaceutics · 2020Review
- Inter-individual and inter-regional variations in enteric drug metabolizing enzyme activities: Results with cryopreserved human intestinal mucosal epithelia (CHIM) from the small intestines of 14 donors.Pharmacology research & perspectives · 2020Article
- Quantitative Proteomics of Clinically Relevant Drug-Metabolizing Enzymes and Drug Transporters and Their Intercorrelations in the Human Small Intestine.Drug metabolism and disposition: the biological fate of chemicals · 2020Observational
- A Pilot Study towards the Impact of Type 2 Diabetes on the Expression and Activities of Drug Metabolizing Enzymes and Transporters in Human Duodenum.International journal of molecular sciences · 2019Article
- Activity and mRNA expression levels of selected cytochromes P450 in various sections of the human small intestine.British journal of clinical pharmacology · 2019Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimsTo characterize mRNA expression levels (17 cytochromes P450) and activity (9 isoforms) of major cytochromes P450 expressed throughout the human small intestine.
methodsTissue samples were obtained from 9 deceased subjects and intestinal sections (n = 10) were isolated for each subject. Relative mRNA expression levels were determined using quantitative real-time PCR. Intestinal microsomes were prepared from 5 subsections: duodenum, jejunum (proximal and mid-jejunum) and ileum (proximal and mid-ileum) regions. In vitro incubations were performed with various cytochrome P450 probe substrates: bupropion (CYP2B6), repaglinide (CYP2C8), tolbutamide (CYP2C9), S-mephenytoin (CYP2C19), bufuralol (CYP2D6), chlorzoxazone (CYP2E1), ebastine (CYP2J2), midazolam (CYP3A4/5) and lauric acid (CYP4A11). Metabolite formation was assessed using validated liquid chromatography-tandem mass spectrometry assays.
resultsCytochrome P450 mRNA levels ranked as follows: CYP3A4 > CYP2C9 > CYP2C19 > CYP2J2 > CYP4F2. Cytochrome P450 mRNA transcripts showed different patterns in their relative expression from 1 region to the other but CYP3A4, CYP2C9, CYP2C19 and CYP2J2 displayed the highest levels of mRNA expression (>5%) in all intestinal sections. Cytochrome P450 activities were greater in proximal part of the small intestine with the jejunum showing the greatest drug-metabolism activity. Spearman's correlation analyses indicated that cytochrome P450 mRNA expressions and corresponding cytochrome P450 activities in the human intestine were moderately associated for CYP2C19, CYP2D6 and CYP4A11 (r
conclusionsOur study provides new and additional information on the expression and activities of selected cytochromes P450 in various sections of the human small intestine.
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