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However, accurately predicting individual exposure in healthy subjects remains challenging due to\u00a0limited data on protein levels throughout the gastrointestinal tract within the same individuals and inadequate assessment of factors influencing these levels. Therefore, we conducted a clinical study to obtain biopsy samples from 8 different gastrointestinal segments in 24 healthy Chinese volunteers. Concurrently, blood and fecal samples were collected for genotypic analysis and fecal microbiota metagenomic sequencing. Using an optimized LC\u2013MS\/MS method, we quantified the absolute protein abundance of CYP2C9, CYP2C19, CYP2D6, CYP3A4, P\u2010gp, and BCRP from the stomach to the colon. Our results revealed significant regional differences in protein expression: CYP3A4 was the most abundant in the small intestine, whereas CYP2C9 was predominantly found in the colon. CYP2D6 was primarily located in the ileum, while other DMEs\/DTs showed higher concentrations in the jejunum. Meanwhile, the enzyme abundance in the small intestine and colon and the relative ratio of transporters in different regions to the jejunum were accurately calculated, providing\u00a0valuable data for refining the physiological parameters in the virtual gastrointestinal tract of Chinese healthy population in PBBMs. Additionally, BMI, IBW, sex, age, genotype, and fecal microbiota were identified as critical factors influencing the protein levels of these DMEs\/DTs throughout the gastrointestinal tract, with notable regional differences. Consequently, this study provides a unique foundation for understanding xenobiotic absorption in humans.<\/jats:p>","DOI":"10.1002\/cpt.3497","type":"journal-article","created":{"date-parts":[[2024,11,25]],"date-time":"2024-11-25T06:53:54Z","timestamp":1732517634000},"page":"676-689","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Distribution Characteristics and Impacting Factors of Drug CYP Enzymes and Transporters in the Gastrointestinal Tract of Chinese Healthy Subjects"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6132-133X","authenticated-orcid":false,"given":"Miao","family":"Zhang","sequence":"first","affiliation":[{"name":"Drug Clinical Trial Center Peking University Third Hospital  Beijing China"},{"name":"Department of Pharmaceutical Sciences, School of Pharmacy, Bouve College of Health Sciences Northeastern University  Boston Massachusetts 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