ReviewThe AAPS journal2016
Gut Wall Metabolism. Application of Pre-Clinical Models for the Prediction of Human Drug Absorption and First-Pass Elimination.
Review in The AAPS journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 57 citations in OpenAlex.
- UniORV, a New Multi-Unit Dosage Form, Improved Biopharmaceutical Properties of Tacrolimus in Rats and Humans.Pharmaceutical research · 2020Trial
- α-Ketoglutarate accelerates cutaneous wound healing through modulating the epithelial-fibroblast niche.JCI insight · 2026Article
- Targeting tumor-associated bacteria in digestive system cancers: carcinogenic mechanisms and nano-regulate platform design.Journal of nanobiotechnology · 2026Review
- Potential Links Between Aging, Mitochondrial Dysfunction, and Drug Transporter Function-Molecular Mechanisms and Pharmacokinetic Implications.International journal of molecular sciences · 2026Review
- Mechanistic evidence for dibutyl phthalate as an environmental trigger for inflammatory bowel disease.iScience · 2026Article
- A primary human Gut/Liver microphysiological system to estimate human oral bioavailability.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Human Small Intestinal Tissue Models to Assess Barrier Permeability: Comparative Analysis of Caco-2 Cells, Jejunal and Duodenal Enteroid-Derived Cells, and EpiIntestinalBioengineering (Basel, Switzerland) · 2025Article
- Recent development of micro-nano carriers for oral antineoplastic drug delivery.Materials today. Bio · 2025Review
- Static Versus Dynamic Model Predictions of Competitive Inhibitory Metabolic Drug-Drug Interactions via Cytochromes P450: One Step Forward and Two Steps Backwards.Clinical pharmacokinetics · 2025Article
- Drug Delivery Across the Blood-Brain Barrier: A New Strategy for the Treatment of Neurological Diseases.Pharmaceutics · 2024Review
- Development of 3D-Bioprinted Colitis-Mimicking Model to Assess Epithelial Barrier Function Using Albumin Nano-Encapsulated Anti-Inflammatory Drugs.Biomimetics (Basel, Switzerland) · 2023Article
- IVIVE: Facilitating the Use ofToxics · 2022Review
- Latest impact of engineered human liver platforms on drug development.APL bioengineering · 2021Review
- PBPK Modeling as a Tool for Predicting and Understanding Intestinal Metabolism of Uridine 5'-Diphospho-glucuronosyltransferase Substrates.Pharmaceutics · 2021Review
- Drug Screening, Oral Bioavailability and Regulatory Aspects: A Need for Human Organoids.Pharmaceutics · 2021Review
- Characterization of P-Glycoprotein Inhibitors for Evaluating the Effect of P-Glycoprotein on the Intestinal Absorption of Drugs.Pharmaceutics · 2021Article
- Quantitative characterization of UDP-glucuronosyltransferase 2B17 in human liver and intestine and its role in testosterone first-pass metabolism.Biochemical pharmacology · 2018Article
- Semimechanistic Population Pharmacokinetic Model to Predict the Drug-Drug Interaction Between S-ketamine and Ticlopidine in Healthy Human Volunteers.CPT: pharmacometrics & systems pharmacology · 2018Article
- Bioprinted 3D Primary Human Intestinal Tissues Model Aspects of Native Physiology and ADME/Tox Functions.iScience · 2018Article
- Molecular Docking-Based Design and Development of a Highly Selective Probe Substrate for UDP-glucuronosyltransferase 1A10.Molecular pharmaceutics · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Quantifying the multiple processes which control and modulate the extent of oral bioavailability for drug candidates is critical to accurate projection of human pharmacokinetics (PK). Understanding how gut wall metabolism and hepatic elimination factor into first-pass clearance of drugs has improved enormously. Typically, the cytochrome P450s, uridine 5'-diphosphate-glucuronosyltransferases and sulfotransferases, are the main enzyme classes responsible for drug metabolism. Knowledge of the isoforms functionally expressed within organs of first-pass clearance, their anatomical topology (e.g. zonal distribution), protein homology and relative abundances and how these differ across species is important for building models of human metabolic extraction. The focus of this manuscript is to explore the parameters influencing bioavailability and to consider how well these are predicted in human from animal models or from in vitro to in vivo extrapolation. A unique retrospective analysis of three AstraZeneca molecules progressed to first in human PK studies is used to highlight the impact that species differences in gut wall metabolism can have on predicted human PK. Compared to the liver, pharmaceutical research has further to go in terms of adopting a common approach for characterisation and quantitative prediction of intestinal metabolism. A broad strategy is needed to integrate assessment of intestinal metabolism in the context of typical DMPK activities ongoing within drug discovery programmes up until candidate drug nomination.
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What OpenQuestion holds
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.