ArticleOncogene2007
Inhibition of drug metabolism by blocking the activation of nuclear receptors by ketoconazole.
Article in Oncogene, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 2 of them syntheses that pooled it.
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
88 citing papers in PubMed, 2 syntheses or guidelines pooled it, 208 citations in OpenAlex.
- Medications That Regulate Pregnane X Receptor: A Systematic Review of Current Evidence.Pharmacology research & perspectives · 2026Pooled it
- Drug-vitamin D interactions: a systematic review of the literature.Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition · 2013Pooled it
- Effect of the CYP3A inhibitor ketoconazole on the PXR-mediated induction of CYP3A activity.European journal of clinical pharmacology · 2013Trial
- Sulforaphane is not an effective antagonist of the human pregnane X-receptor in vivo.Toxicology and applied pharmacology · 2013Trial
- Article
- Discovery of PXR Antagonist MI891 and PXR Degrader MI1013 and Their Roles in Hepatic Gene Regulation.Journal of medicinal chemistry · 2025Article
- The Effect of Concomitant Administration of Proton Pump Inhibitors on the Pharmacokinetics of CDK4/6 Inhibitors in Rats: Implications for the Evaluation of Hepatic and Transporter-Mediated Drug-Drug Interactions.European journal of drug metabolism and pharmacokinetics · 2024Article
- Importance of ABC Transporters in the Survival of Parasitic Nematodes and the Prospect for the Development of Novel Control Strategies.Pathogens (Basel, Switzerland) · 2023Review
- Interaction of pregnane X receptor with hypoxia-inducible factor-1 regulates chemoresistance of prostate cancer cells.Cancer drug resistance (Alhambra, Calif.) · 2023Article
- Article
- Review
- Niclosamide induces miR-148a to inhibit PXR and sensitize colon cancer stem cells to chemotherapy.Stem cell reports · 2022Article
- Article
- Pregnane X Receptor and the Gut-Liver Axis: A Recent Update.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Mechanistically Coupled PK (MCPK) Model to Describe Enzyme Induction and Occupancy Dependent DDI of Dabrafenib Metabolism.Pharmaceutics · 2022Article
- Article
- Insights into the critical role of the PXR in preventing carcinogenesis and chemotherapeutic drug resistance.International journal of biological sciences · 2022Review
- Gadd45 in the Liver: Signal Transduction and Transcriptional Mechanisms.Advances in experimental medicine and biology · 2022Article
- Modulation of the Blood-Brain Barrier for Drug Delivery to Brain.Pharmaceutics · 2021Review
- A Literature Review of the Potential Impact of Medication on Vitamin D Status.Risk management and healthcare policy · 2021Review
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Individual variation in drug metabolism is a major cause of unpredictable side effects during therapy. Drug metabolism is controlled by a class of orphan nuclear receptors (NRs), which regulate expression of genes such as CYP (cytochrome)3A4 and MDR-1 (multi-drug resistance-1), that are involved in this process. We have found that xenobiotic-mediated induction of CYP3A4 and MDR-1 gene transcription was inhibited by ketoconazole, a commonly used antifungal drug. Ketoconazole mediated its effect by inhibiting the activation of NRs, human pregnenolone X receptor and constitutive androstene receptor, involved in regulation of CYP3A4 and MDR-1. The effect of ketoconazole was specific to the group of NRs that control xenobiotic metabolism. Ketoconazole disrupted the interaction of the xenobiotic receptor PXR with the co-activator steroid receptor co-activator-1. Ketoconazole treatment resulted in delayed metabolism of tribromoethanol anesthetic in mice, which was correlated to the inhibition of PXR activation and downmodulation of cyp3a11 and mdr-1 genes and proteins. These studies demonstrate for the first time that ketoconazole represses the coordinated activation of genes involved in drug metabolism, by blocking activation of a specific subset of NRs. Our results suggest that ketoconazole can be used as a pan-antagonist of NRs involved in xenobiotic metabolism in vivo, which may lead to novel strategies that improve drug effect and tolerance.
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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.