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The PXR protein is also an orphan nuclear receptor with a broad spectrum of potential ligands, including common prescription drugs, that can act as agonists or antagonists. Once activated, PXR upregulates several target genes involved in xenobiotic metabolism and can influence lipid and glucose metabolism, as well as the metabolism of commonly used drugs. In this review we searched the primary literature for articles reporting on drugs that regulate PXR and discuss potential clinical implications. Using the databases CINAHL, Embase, Medline, Scopus and Web of Science, we searched for terms related to PXR, following PRISMA guidelines. We screened 12\u2009236 studies, 101 of which met the inclusion criteria, and included a further 46 research and review articles. We identified 42 studies reporting on prescription medications and 40 on non\u2010prescription medications that regulate PXR as agonists or antagonists, and 47 studies reporting both beneficial and detrimental PXR\u2010mediated effects of drugs on specific diseases, including different cancers, metabolic diseases, and inflammatory conditions, among others. We conclude that PXR is regulated by a broad range of drugs. Downstream effects of this regulation affect different diseases, leading to clinically relevant outcomes, such as altered efficacy of drugs or changes to the pathophysiology of a disease. Understanding and managing the agonist or antagonist role of drugs on PXR holds great potential to improve the health outcomes of different diseases. However, more information is needed about the potency of known PXR regulators.<\/jats:p>","DOI":"10.1002\/prp2.70288","type":"journal-article","created":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T10:01:58Z","timestamp":1784023318000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Medications That Regulate Pregnane X Receptor: A Systematic Review of Current Evidence"],"prefix":"10.1002","volume":"14","author":[{"given":"Petra","family":"Czarniak","sequence":"first","affiliation":[{"name":"Curtin Medical School, Faculty of Health Sciences Curtin University  Bentley Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael","family":"Moorin","sequence":"additional","affiliation":[{"name":"Curtin School of Population Health Curtin University  Perth Western Australia 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