ArticleBritish journal of clinical pharmacology2025
Variability in intestinal drug metabolizing enzymes and transporters in Crohn's disease and potential impact on oral drug absorption.
Article in British journal of clinical pharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
5 citing papers in PubMed.
- Engineering human Gut-on-a-Chip culturomics for predictive pharmacomicrobiomics of first-pass metabolism.npj biomedical innovations · 2026Review
- Interactions between long-acting antiretrovirals and opioids: a call for clinical awareness.Clinical microbiology reviews · 2026Review
- Application of New Approach Methodologies to Improve Oral Biopharmaceutic Assessments.Pharmaceutics · 2026Review
- Effect of proinflammatory cytokines on intestinal drug transporters in human enteroid monolayers.Drug metabolism and disposition: the biological fate of chemicals · 2026Article
- Variability in intestinal drug metabolizing enzymes and transporters in Crohn's disease and potential impact on oral drug absorption.British journal of clinical pharmacology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
Abstract
aimsThe aim of study was to generate quantitative data on the abundance of drug-metabolizing enzymes and transporters (DMETs) in inflamed and non-inflamed Crohn's disease (CD) ileum and colon, for incorporation into physiologically based pharmacokinetic (PBPK) models, enabling prediction of oral drugs' pharmacokinetics (PK) perturbation in CD patients.
methodsHomogenate fractions were processed from 13 inflamed (six ileum and seven colon) and seven non-inflamed (two ileum and five colon) CD and 10 healthy (five ileum and five colon) tissues from deceased subjects by calcium chelation elution, and protein abundances determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based proteomics and compared with healthy values. PBPK simulation was applied to predict the potential effect of altered DMET profiles on the PK of oral drugs.
resultsAll investigated proteins showed trends for reduced expression in inflamed and non-inflamed CD samples relative to healthy individuals. Significant downregulation (P < 0.05) was observed for CYP3A4, AOX1, NAT1 and several SULTs in inflamed ileum as well as UGT1A10, NAT1, BCRP and several SULTs in inflamed and non-inflamed colon. Inter-individual variability was generally higher in CD, with exceptions, for most targets (up to 146%CV in inflamed ileum and up to 169% in histologically normal colon tissues). Integration of abundance data into a verified PBPK model of CD showed a considerable (≥2-fold; CD predicted relative to healthy predicted) change in systemic drug exposure for 10 drugs examined.
conclusionsCD inflammation significantly suppresses the expression of intestinal DMETs, which, together with changes in other system parameters, can alter the fate of drugs taken orally in these patients. Virtual patients within a PBPK framework, informed by the measured DMET ranges in the intestine, may serve as a guide for dose adjustment in the absence of dedicated clinical studies.
Indexed as
Identifiers
What Socratic 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 Socratic graph.