{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T14:26:06Z","timestamp":1768314366843,"version":"3.49.0"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Sirolimus is primarily metabolized by CYP3A4 and transported by P-gp. Drug interactions that affect this pathway can alter its plasma exposures, resulting in untargeted sirolimus concentrations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case summary<\/jats:title><jats:p>In this case report, we investigate a pharmacokinetic drug-drug interaction between regorafenib and sirolimus, mediated by CYP3A4 and P-gp, in a 56-year-old Chinese male with recurrent hepatocellular carcinoma post-liver transplantation. In this case, the patient\u2019s baseline sirolimus trough blood concentration was 5.0\u00a0ng\/mL prior to initiating a new cycle of regorafenib (80\u00a0mg once daily). Following a 7-day administration period of regorafenib, a notable elevation in sirolimus trough blood concentration to 12.3\u00a0ng\/mL was observed. Upon cessation of regorafenib therapy for one week, the sirolimus trough blood concentration reverted back to 5.2\u00a0ng\/mL. Nevertheless, upon resumption of regorafenib (160\u00a0mg once daily) treatment for an additional 10\u00a0days, the sirolimus trough blood concentration experienced a recurrence of increase, reaching 11.0\u00a0ng\/mL. Following the confirmation of tumor progression, the discontinuation of regorafenib was deemed necessary. Consequently, a subsequent medical evaluation of the patient\u2019s sirolimus trough blood concentration, undertaken precisely one month after cessation of regorafenib therapy, revealed a concentration level of 2.8\u00a0ng\/mL. Based on the Drug Interaction Probability Scale, this interaction was deemed probable.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Regorafenib exerts a regulatory influence on the blood concentrations of sirolimus by inhibiting the activity of CYP3A4 and P-gp, potentially altering its pharmacokinetic profile. Given the potential for both excessive and inadequate immunosuppression to adversely affect patients with recurrent hepatocellular carcinoma post-liver transplantation, clinicians must maintain a heightened awareness of this drug-drug interaction.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fphar.2025.1472896","type":"journal-article","created":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T06:48:45Z","timestamp":1739947725000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Case report: Pharmacokinetic interaction involving sirolimus and regorafenib in patients with post-transplant recurrent hepatocellular carcinoma"],"prefix":"10.3389","volume":"16","author":[{"given":"Kongcai","family":"Zhu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Xiong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Haihong","family":"Bai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,19]]},"reference":[{"key":"B1","unstructured":"Australian Public Assessment Report for Regorafenib (tga.gov.au)\n          \n          \n          2014"},{"key":"B2","unstructured":"Everolimus (afinitor): summary of product characteristics"},{"key":"B3","unstructured":"Regorafenib (stivarga): summary of product characteristics"},{"key":"B4","unstructured":"Sirolimus (rapamune): summary of product characteristics"},{"key":"B5","doi-asserted-by":"publisher","first-page":"765","DOI":"10.3969\/j.issn.1674-7445.2023167","article-title":"Chinese expert consensus on clinical application of inhibitors of mammalian target of rapamycin in liver transplant recipients (2023 edition)","volume":"14","author":"Feng","year":"2023","journal-title":"ORGAN Transplant."},{"key":"B6","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1097\/tp.0b013e3181fe131b","article-title":"Switching to sirolimus-based immune suppression after liver transplantation is safe and effective: a single-center experience","volume":"91","author":"Harper","year":"2011","journal-title":"Transplantation"},{"key":"B7","doi-asserted-by":"publisher","first-page":"674","DOI":"10.1345\/aph.1H423","article-title":"Proposal for a new tool to evaluate drug interaction cases","volume":"41","author":"Horn","year":"2007","journal-title":"Ann. 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Int."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1472896\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T06:48:52Z","timestamp":1739947732000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1472896\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,19]]},"references-count":17,"alternative-id":["10.3389\/fphar.2025.1472896"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1472896","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,19]]},"article-number":"1472896"}}