ArticleClinical pharmacology and therapeutics2022
Drug Disposition Protein Quantification in Matched Human Jejunum and Liver From Donors With Obesity.
Article in Clinical pharmacology and therapeutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- PBPK modeling: What is the role of CYP3A4 expression in the gastrointestinal tract to accurately predict first-pass metabolism?CPT: pharmacometrics & systems pharmacology · 2025Pooled it
- Application of Virtual Twin PBPK Models in Individuals with Obesity via CYP3A4 Phenotyping Using Endogenous Biomarker Data.Clinical pharmacology and therapeutics · 2026Article
- Deconvoluting Gut Versus Liver Cytochrome P450 3A4 Function: Drug Probes, Biomarkers, and Tissue Biopsy.Journal of clinical pharmacology · 2026Review
- Virtual Twin-PBPK Modelling: A Step Toward Precision Dosing in Patients with Obesity.The AAPS journal · 2026Article
- Target Abundance in Pharmacological Target-Mediated Drug Disposition (TMDD) for Small Molecules - A Proteomics Approach.The AAPS journal · 2026Article
- Development of a PBPK Model for Lamotrigine which Incorporates Metabolism by UGT2B10: Impact of UGT2B10 Poor Metabolizer Phenotype and Pregnancy.The AAPS journal · 2025Article
- Effects of Chronic Alcohol Intake on the Composition of the Ensemble of Drug-Metabolizing Enzymes and Transporters in the Human Liver.Journal of xenobiotics · 2025Article
- Personalized Medicine Approach to Proteomics and Metabolomics of Cytochrome P450 Enzymes: A Narrative Review.European journal of drug metabolism and pharmacokinetics · 2024Review
- Recent Advances on the Regulations of Organic Anion Transporters.Pharmaceutics · 2024Review
- A guide to developing population files for physiologically-based pharmacokinetic modeling in the Simcyp Simulator.CPT: pharmacometrics & systems pharmacology · 2024Article
- Illuminating the function of the orphan transporter, SLC22A10, in humans and other primates.Nature communications · 2024Article
- Effects of alcohol consumption and tobacco smoking on the composition of the ensemble of drug metabolizing enzymes and transporters in human liver.bioRxiv : the preprint server for biology · 2024Article
- In Vitro to In Vivo Scalars for Drug Clearance in Nonalcoholic Fatty Liver and Steatohepatitis.Drug metabolism and disposition: the biological fate of chemicals · 2024Article
- Digoxin Pharmacokinetics in Patients with Obesity Before and After a Gastric Bypass or a Strict Diet Compared with Normal Weight Individuals.Clinical pharmacokinetics · 2024Article
- Simultaneous Prediction Method for Intestinal Absorption and Metabolism Using the Mini-Ussing Chamber System.Pharmaceutics · 2023Review
- Quantitative Translation of Substrate Intrinsic Clearance from Recombinant CYP1A1 to Humans.The AAPS journal · 2023Article
- Illuminating the Function of the Orphan Transporter, SLC22A10 in Humans and Other Primates.Research square · 2023Article
- Illuminating the Function of the Orphan Transporter, SLC22A10 in Humans and Other Primates.bioRxiv : the preprint server for biology · 2023Article
- Impact of type 2 diabetes on in vivo activities and protein expressions of cytochrome P450 in patients with obesity.Clinical and translational science · 2022Article
- Correlations between 4β-hydroxycholesterol and hepatic and intestinal CYP3A4: protein expression, microsomal ex vivo activity, and in vivo activity in patients with a wide body weight range.European journal of clinical pharmacology · 2022Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mathematical models, such as physiologically-based pharmacokinetic models, are used to predict, for example, drug disposition and toxicity. However, populations differ in the abundance of proteins involved in these processes. To improve the building and refinement of such models, they must take into account these interindividual variabilities. In this study, we used global proteomics to characterize the protein composition of jejunum and liver from 37 donors with obesity enrolled in the COCKTAIL study. Liver protein levels from the 37 donors were further compared with those from donors without obesity. We quantified thousands of proteins and could present the expression of several drug-metabolizing enzymes, for the first time, in jejunum, many of which belong to the cytochrome P450 (CYP) (e.g., CYP2U1) and the amine oxidase (flavin-containing) (e.g., monoamine oxidase A (MAOA)) families. Although we show that many metabolizing enzymes had greater expression in liver, others had higher expression in jejunum (such as, MAOA and CES2), indicating the role of the small intestine in extrahepatic drug metabolism. We further show that proteins involved in drug disposition are not correlated in the two donor-matched tissues. These proteins also do not correlate with physiological factors such as body mass index, age, and inflammation status in either tissue. Furthermore, the majority of these proteins are not differently expressed in donors with or without obesity. Nonetheless, interindividual differences were considerable, with implications for personalized prediction models and systems pharmacology.
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