ReviewClinical pharmacokinetics2016
Predicting Drug Extraction in the Human Gut Wall: Assessing Contributions from Drug Metabolizing Enzymes and Transporter Proteins using Preclinical Models.
Review in Clinical pharmacokinetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
37 citing papers in PubMed, 99 citations in OpenAlex.
- Biopharmaceutical Characterization of Grapiprant Within the BCS Framework Under Canine-Relevant Conditions: Solubility and Caco-2 Permeability Assessment.Pharmaceutics · 2026Article
- Engineering human Gut-on-a-Chip culturomics for predictive pharmacomicrobiomics of first-pass metabolism.npj biomedical innovations · 2026Review
- Impact of Preclinical Verification in Physiologically Based Pharmacokinetic Modelling for First-in-Human Predictions: Application of a Published Model Building Strategy for Five Compounds.Clinical pharmacokinetics · 2026Article
- Hepatitis E virus replication is maintained in proliferative cells within the intestinal crypt.Science advances · 2026Article
- Biomarker-Guided Drug Delivery Systems and Oral Bioavailability Enhancement.Pharmaceuticals (Basel, Switzerland) · 2026Review
- A primary human Gut/Liver microphysiological system to estimate human oral bioavailability.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Article
- Robust and reproducible human intestinal organoid-derived monolayer model for analyzing drug absorption.Scientific reports · 2025Article
- Evaluation of Solubility-Limited Absorption as a Surrogate to Predicting Positive Food Effect of BCS II/IV Drugs.Clinical pharmacokinetics · 2025Article
- Simultaneous Prediction Method for Intestinal Absorption and Metabolism Using the Mini-Ussing Chamber System.Pharmaceutics · 2023Review
- Development of 3D-Bioprinted Colitis-Mimicking Model to Assess Epithelial Barrier Function Using Albumin Nano-Encapsulated Anti-Inflammatory Drugs.Biomimetics (Basel, Switzerland) · 2023Article
- Generation of Caco-2 cells stably expressing CYP3A4·POR·UGT1A1 and CYP3A4·POR·UGT1A1*6 using a PITCh system.Archives of toxicology · 2022Article
- Impact of gastrointestinal differences in veterinary species on the oral drug solubility, in vivo dissolution, and formulation of veterinary therapeutics.ADMET & DMPK · 2022Article
- PBK Model-Based Prediction of Intestinal Microbial and Host Metabolism of Zearalenone and Consequences for its Estrogenicity.Molecular nutrition & food research · 2021Article
- PBPK Modeling as a Tool for Predicting and Understanding Intestinal Metabolism of Uridine 5'-Diphospho-glucuronosyltransferase Substrates.Pharmaceutics · 2021Review
- Potential Applications of Chitosan-Based Nanomaterials to Surpass the Gastrointestinal Physiological Obstacles and Enhance the Intestinal Drug Absorption.Pharmaceutics · 2021Review
- Article
- Parameterization of Microsomal and Cytosolic Scaling Factors: Methodological and Biological Considerations for Scalar Derivation and Validation.European journal of drug metabolism and pharmacokinetics · 2021Article
- Cytochrome P450 expression, induction and activity in human induced pluripotent stem cell-derived intestinal organoids and comparison with primary human intestinal epithelial cells and Caco-2 cells.Archives of toxicology · 2021Article
- Evaluation of Barrier Functions in Human iPSC-Derived Intestinal Epithelium.Methods in molecular biology (Clifton, N.J.) · 2021Article
Corrections and comments
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Authors and funding
4 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Intestinal metabolism can limit oral bioavailability of drugs and increase the risk of drug interactions. It is therefore important to be able to predict and quantify it in drug discovery and early development. In recent years, a plethora of models-in vivo, in situ and in vitro-have been discussed in the literature. The primary objective of this review is to summarize the current knowledge in the quantitative prediction of gut-wall metabolism. As well as discussing the successes of current models for intestinal metabolism, the challenges in the establishment of good preclinical models are highlighted, including species differences in the isoforms; regional abundances and activities of drug metabolizing enzymes; the interplay of enzyme-transporter proteins; and lack of knowledge on enzyme abundances and availability of empirical scaling factors. Due to its broad specificity and high abundance in the intestine, CYP3A is the enzyme that is frequently implicated in human gut metabolism and is therefore the major focus of this review. A strategy to assess the impact of gut wall metabolism on oral bioavailability during drug discovery and early development phases is presented. Current gaps in the mechanistic understanding and the prediction of gut metabolism are highlighted, with suggestions on how they can be overcome in the future.
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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.