ArticleDrug metabolism and disposition: the biological fate of chemicals2008
A comprehensive in vitro and in silico analysis of antibiotics that activate pregnane X receptor and induce CYP3A4 in liver and intestine.
Article in Drug metabolism and disposition: the biological fate of chemicals, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers, 2 of them syntheses that pooled it.
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.
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Who cites it
35 citing papers in PubMed, 2 syntheses or guidelines pooled it, 79 citations in OpenAlex.
- Medications That Regulate Pregnane X Receptor: A Systematic Review of Current Evidence.Pharmacology research & perspectives · 2026Pooled it
- Antibiotic treatment for the sexual partners of women with bacterial vaginosis.The Cochrane database of systematic reviews · 2016Pooled it
- Dicloxacillin is an inducer of intestinal P-glycoprotein but neither dicloxacillin nor flucloxacillin increases the risk of stroke/systemic embolism in direct oral anticoagulant users.British journal of clinical pharmacology · 2024Trial
- Dicloxacillin induces CYP2C19, CYP2C9 and CYP3A4 in vivo and in vitro.British journal of clinical pharmacology · 2018Trial
- PXR polymorphisms and their impact on pharmacokinetics/pharmacodynamics of repaglinide in healthy Chinese volunteers.European journal of clinical pharmacology · 2013Trial
- The Effect of Dicloxacillin Administration on Pharmacokinetics of Narrow Therapeutic Window Drugs: Phenytoin and Warfarin.Clinical pharmacology and therapeutics · 2026Article
- Gefitinib-Induced Severe Dermatological Adverse Reactions: A Case Report and Pharmacogenetic Profile.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Drug Repurposing: A Leading Strategy for New Threats and Targets.ACS pharmacology & translational science · 2024Review
- Article
- Interaction between posaconazole and flucloxacillin in a lung transplant patient: decrease in plasma exposure of posaconazole and possible undertreatment of invasive aspergillosis: case report.BMC pulmonary medicine · 2022Article
- Jekyll and Hyde: nuclear receptors ignite and extinguish hepatic oxidative milieu.Trends in endocrinology and metabolism: TEM · 2021Review
- Identification of novel pregnane X receptor (PXR) agonists by In silico and biological activity analyses and reversal of cigarette smoke-induced PXR downregulation.Biochemical and biophysical research communications · 2021Article
- The Interplay of ABC Transporters in Aβ Translocation and Cholesterol Metabolism: Implicating Their Roles in Alzheimer's Disease.Molecular neurobiology · 2021Review
- Computational drug repurposing for inflammatory bowel disease using genetic information.Computational and structural biotechnology journal · 2019Article
- Significant drug-drug interaction between warfarin and nafcillin.Therapeutic advances in drug safety · 2018Article
- Echinocandins for management of invasive candidiasis in patients with liver disease and liver transplantation.Infection and drug resistance · 2018Review
- Pharmacogenomics of CYP2C9: Functional and Clinical Considerations.Journal of personalized medicine · 2017Review
- Role of the CYP3A4-mediated 11,12-epoxyeicosatrienoic acid pathway in the development of tamoxifen-resistant breast cancer.Oncotarget · 2017Article
- Article
- Solithromycin Pharmacokinetics in Plasma and Dried Blood Spots and Safety in Adolescents.Antimicrobial agents and chemotherapy · 2016Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
We have investigated several in silico and in vitro methods to improve our ability to predict potential drug interactions of antibiotics. Our focus was to identify those antibiotics that activate pregnane X receptor (PXR) and induce CYP3A4 in human hepatocytes and intestinal cells. Human PXR activation was screened using reporter assays in HepG2 cells, kinetic measurements of PXR activation were made in DPX-2 cells, and induction of CYP3A4 expression and activity was verified by quantitative polymerase chain reaction, immunoblotting, and testosterone 6beta-hydroxylation in primary human hepatocytes and LS180 cells. We found that in HepG2 cells CYP3A4 transcription was activated strongly (> 10-fold) by rifampin and troleandomycin; moderately (> or = 7-fold) by dicloxacillin, tetracycline, clindamycin, griseofulvin, and (> or = 4-fold) erythromycin; and weakly (> 2.4-fold) by nafcillin, cefaclor, sulfisoxazole, and (> 2-fold) cefadroxil and penicillin V. Similar although not identical results were obtained in DPX-2 cells. CYP3A4 mRNA and protein expression were induced by these antibiotics to differing extents in both liver and intestinal cells. CYP3A4 activity was significantly increased by rifampin (9.7-fold), nafcillin and dicloxacillin (5.9-fold), and weakly induced (2-fold) by tetracycline, sufisoxazole, troleandomycin, and clindamycin. Multiple pharmacophore models and docking indicated a good fit for dicloxacillin and nafcillin in PXR. These results suggest that in vitro and in silico methods can help to prioritize and identify antibiotics that are most likely to reduce exposures of medications (such as oral contraceptive agents) which interact with enzymes and transporters regulated by PXR. In summary, nafcillin, dicloxacillin, cephradine, tetracycline, sulfixoxazole, erythromycin, clindamycin, and griseofulvin exhibit a clear propensity to induce CYP3A4 and warrant further clinical investigation.
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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.