{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:55:37Z","timestamp":1787068537490,"version":"build-2736575974"},"reference-count":35,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T00:00:00Z","timestamp":1731456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:p>\n                    Dexamethasone (DEX) is currently the treatment of choice for patients with oxygen\u2010dependent COVID\u201019. It has been observed, primarily\n                    <jats:italic>in vitro<\/jats:italic>\n                    , that dexamethasone induces the expression of CYP3A and the ABCB1 gene, which encodes P\u2010glycoprotein (P\u2010gp). This has raised concerns about potential interactions between DEX and substrates of CYP3A and P\u2010gp, such as direct oral anticoagulants (DOAC). Currently, there is limited robust evidence to support a clinically significant interaction between DEX and DOAC. Using physiologically based pharmacokinetic modeling (PBPK), we investigated the impact of DEX administered in the context of SARS\u2010CoV\u20102 infection on the pharmacokinetics of apixaban (APX) and rivaroxaban (RVX). After validating the induction effect of the DEX compound on two CYP3A4 substrates using the limited available studies, we optimized the compound in a COVID\u201019 patient population, where significantly higher DEX plasma concentrations were observed compared to healthy volunteers. Our PBPK\u2010based PK simulations showed a 20% decrease in the AUC of APX and RVX in a worst\u2010case scenario and when DEX was administered at 6\u2009mg PO for 10\u2009days. This finding confirms the limited clinical data currently available and supports the use of APX and RVX with DEX in COVID\u201019 patients at low\u2010risk for thrombo\u2010embolism. In addition, our results suggest that prednisone (PRED), when used at an equipotent dose, could serve as a viable alternative to DEX, given its less pronounced induction effect on APX and RVX. Further research is needed to validate these findings and to explore the clinical implications of using PRED in place of DEX in such scenarios.\n                  <\/jats:p>","DOI":"10.1002\/cpt.3491","type":"journal-article","created":{"date-parts":[[2024,11,13]],"date-time":"2024-11-13T07:38:05Z","timestamp":1731483485000},"page":"554-560","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["The Impact of Dexamethasone and Prednisone on Apixaban and Rivaroxaban Exposure in COVID\u201019 Patients: A Physiologically Based Pharmacokinetic Modeling Study"],"prefix":"10.1002","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5878-4878","authenticated-orcid":false,"given":"Jean","family":"Terrier","sequence":"first","affiliation":[{"name":"Division of Clinical Pharmacology and Toxicology Geneva University Hospitals  Geneva Switzerland"},{"name":"Faculty of Medicine University of Geneva  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4401-432X","authenticated-orcid":false,"given":"Kenza","family":"Abouir","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and Toxicology Geneva University Hospitals  Geneva Switzerland"},{"name":"Faculty of Medicine University of Geneva  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0225-7294","authenticated-orcid":false,"given":"Frederic","family":"Gaspar","sequence":"additional","affiliation":[{"name":"Center for Research and Innovation in Clinical Pharmaceutical Sciences Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"},{"name":"Service of Clinical Pharmacology Lausanne University Hospital and University of Lausanne  Lausanne Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7497-5359","authenticated-orcid":false,"given":"Youssef","family":"Daali","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and Toxicology Geneva University Hospitals  Geneva Switzerland"},{"name":"Faculty of Medicine University of Geneva  Geneva Switzerland"},{"name":"School of Pharmaceutical Sciences, Institute of Pharmaceutical Sciences of Western Switzerland University of Geneva  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8178-0616","authenticated-orcid":false,"given":"Caroline Flora","family":"Samer","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology and Toxicology Geneva University Hospitals  Geneva Switzerland"},{"name":"Faculty of Medicine University of Geneva  Geneva Switzerland"},{"name":"School of Pharmaceutical Sciences, Institute of Pharmaceutical Sciences of Western Switzerland University of Geneva  Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,13]]},"reference":[{"key":"e_1_2_9_1_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciaa478"},{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm12227120"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/10600280211025042"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2021.04.003"},{"key":"e_1_2_9_5_1","unstructured":"Information on COVID\u201019 treatment prevention and research. 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