ArticleThe Journal of clinical investigation2019
Pregnane X receptor activation potentiates ritonavir hepatotoxicity.
Article in The Journal of clinical investigation, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 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
30 citing papers in PubMed, 45 citations in OpenAlex.
- Pharmacokinetic profile and safety of adjusted doses of darunavir/ritonavir with rifampicin in people living with HIV.The Journal of antimicrobial chemotherapy · 2020Trial
- Cytoplasmic PXR regulates glucose metabolism by binding mRNAs and modulating their stability.Nature structural & molecular biology · 2025Article
- COVID-19 Infection, Drugs, and Liver Injury.Journal of clinical medicine · 2025Review
- Exploring Adverse Event Associations of Predicted PXR Agonists Using the FAERS Database.International journal of molecular sciences · 2025Article
- Development and hepatotoxicity of rifamycin derivatives.Expert opinion on drug metabolism & toxicology · 2025Review
- Targeting a distinct binding pocket in the pregnane X receptor with natural agonist TRLW-2 ameliorates murine ulcerative colitis.Frontiers in pharmacology · 2025Article
- Characteristics and mechanisms of liver injury caused by emerging infectious diseases.Frontiers in immunology · 2025Review
- Activation of PXR causes drug interactions with Paxlovid in transgenic mice.Acta pharmaceutica Sinica. B · 2023Article
- Pregnane X receptor (PXR) deficiency protects against spinal cord injury by activating NRF2/HO-1 pathway.CNS neuroscience & therapeutics · 2023Article
- Molecular Factors and Pathways of Hepatotoxicity Associated with HIV/SARS-CoV-2 Protease Inhibitors.International journal of molecular sciences · 2023Review
- Chemical basis of pregnane X receptor activators in the herbal supplement Gancao (licorice).Liver research (Beijing, China) · 2022Article
- COVID-19-induced liver injury in adult patients: A brief overview.World journal of virology · 2022Review
- A literature review of liver function test elevations in rifampin drug-drug interaction studies.Clinical and translational science · 2022Review
- Liver dysfunction during COVID-19 pandemic: Contributing role of associated factors in disease progression and severity.World journal of hepatology · 2022Review
- The Effect of Rifampicin on Darunavir, Ritonavir, and Dolutegravir Exposure within Peripheral Blood Mononuclear Cells: a Dose Escalation Study.Antimicrobial agents and chemotherapy · 2022Article
- Slower Recovery with Early Lopinavir/Ritonavir use in Pediatric COVID-19 Patients: A Retrospective Observational Study.Paediatric drugs · 2022Observational
- Long Noncoding RNAs Hepatocyte Nuclear Factor 4A Antisense RNA 1 and Hepatocyte Nuclear Factor 1A Antisense RNA 1 Are Involved in Ritonavir-Induced Cytotoxicity in Hepatoma Cells.Drug metabolism and disposition: the biological fate of chemicals · 2022Article
- Roles of Cofactors in Drug-Induced Liver Injury: Drug Metabolism and Beyond.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Pregnane X Receptor and the Gut-Liver Axis: A Recent Update.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Identifying Drug-Induced Liver Injury Associated With Inflammation-Drug and Drug-Drug Interactions in Pharmacologic Treatments for COVID-19 by Bioinformatics and System Biology Analyses: The Role of Pregnane X Receptor.Frontiers in pharmacology · 2022Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Ritonavir (RTV) is on the World Health Organization's List of Essential Medicines for antiretroviral therapy, but can cause hepatotoxicity by unknown mechanisms. Multiple clinical studies found that hepatotoxicity occurred in 100% of participants who were pretreated with rifampicin or efavirenz followed by RTV-containing regimens. Both rifampicin and efavirenz are activators of the pregnane X receptor (PXR), a transcription factor with significant inter-species differences in ligand-dependent activation. Using PXR-humanized mouse models, we recapitulated the RTV hepatotoxicity observed in the clinic. PXR was found to modulate RTV hepatotoxicity through CYP3A4-dependent pathways involved in RTV bioactivation, oxidative stress, and endoplasmic reticulum stress. In summary, the current work demonstrated the essential roles of human PXR and CYP3A4 in RTV hepatotoxicity, which can be applied to guide the safe use of RTV-containing regimens in the clinic.
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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.