ArticlePharmacology research & perspectives2020
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.
Article in Pharmacology research & perspectives, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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11 citing papers in PubMed, 20 citations in OpenAlex.
- Canine duodenal organoids as a functional platform for intestinal CYP regulation and drug metabolism studies.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Protein Levels of 16 Cytochrome P450s and 2 Carboxyl Esterases Using Absolute Quantitative Proteomics: CYP2C9 and CYP3A4 Are the Most Abundant Isoforms in Human Liver and Intestine, Respectively.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Hazardous Interactions Between Food, Herbs, and Drugs in the First Stage of Biotransformation: Case Reports of Adverse Drug Interactions in Humans.International journal of molecular sciences · 2025Review
- Probing Liver Injuries Induced by Thioacetamide in Human In Vitro Pooled Hepatocyte Experiments.International journal of molecular sciences · 2024Article
- Recent advances in the translation of drug metabolism and pharmacokinetics science for drug discovery and development.Acta pharmaceutica Sinica. B · 2022Review
- Gutsy science: In vitro systems of the human intestine to model oral drug disposition.Pharmacology & therapeutics · 2022Review
- Analyzing the metabolic fate of oral administration drugs: A review and state-of-the-art roadmap.Frontiers in pharmacology · 2022Review
- Contribution of CYP2D6 Functional Activity to Oxycodone Efficacy in Pain Management: Genetic Polymorphisms, Phenoconversion, and Tissue-Selective Metabolism.Pharmaceutics · 2021Review
- 3D cell culture models: Drug pharmacokinetics, safety assessment, and regulatory consideration.Clinical and translational science · 2021Review
- PBPK Modeling as a Tool for Predicting and Understanding Intestinal Metabolism of Uridine 5'-Diphospho-glucuronosyltransferase Substrates.Pharmaceutics · 2021Review
- 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
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8 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
We have previously reported successful isolation and cryopreservation of human intestinal mucosa (CHIM) with retention of viability and drug metabolizing enzyme activities. Here we report the results of the quantification of drug metabolizing enzyme activities in CHIM from different regions of the small intestines from 14 individual donors. CHIM were isolated from the duodenum, jejunum, and ileum of 10 individuals, and from 10 consecutive 12-inch segments starting from the pyloric sphincter of human small intestines from four additional individuals. P450 and non-P450 drug metabolizing enzyme activities (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A, UGT, SULT, FMO, MAO, AO, NAT1, and NAT2) were quantified via incubation with pathway-selective substrates. Quantifiable activities were observed for all pathways except for CYP2A6. Comparison of the duodenum, jejunum, and ileum in 10 donors shows jejunum had higher activities for CYP2C9, CYP3A, UGT, SULT, MAO, and NAT1. Further definition of regional variations with CHIM from ten 12-inch segments of the proximal small intestine shows that the segments immediately after the first 12-inch segment (duodenum) had the highest activity for most of the drug metabolizing enzymes but with substantial differences among the four donors. Our overall results demonstrate that there are substantial individual differences in drug metabolizing enzymes and that jejunum, especially the regions immediately after the duodenum, had the highest drug metabolizing enzyme activities.
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