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Individualized anticoagulation is crucial in patients with a transjugular intrahepatic portosystemic shunt (TIPS) and portal vein hypercoagulability to avoid stent thrombosis. As TIPS shunts portal blood directly into the systemic circulation and may substantially affect the first-pass extraction\/distribution of direct oral anticoagulants, no population prospective pharmacokinetic studies have been published in patients undergoing TIPS placement so far. The goal of this study was to establish a PopPK model for rivaroxaban in post-TIPS patients, investigate clinical covariate effects on PK, and provide an optimized dosing regimen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this single-centre prospective study, 39 adult patients underwent TIPS and received rivaroxaban 5 or 10\u00a0mg once daily thereafter. Population PK analysis was conducted in NONMEM with 131 plasma concentrations available from 38 evaluable patients (median age: 56 years; median body weight: 63.8\u00a0kg). Parameterized model was then applied to simulate steady-state exposure of 5, 7.5, 10, and 15\u00a0mg once daily regimen.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The final PopPK model was based on a one-compartment with sequential zero-order followed by first-order absorption kinetics, and included the effects of an absorption lag time and linear elimination. The apparent clearance and volume of distribution were 7.48\u00a0L\/h and 4.75\u00a0L, respectively. Based on patient-specific simulations of 38 subjects, at the 5\u00a0mg\/day dose, an exposure within predefined limits was potentially preserved in 96.7% of the cases vs. 62.5% for the 10\u00a0mg\/day (thresholds: AUC\n                      <jats:sub>ss,24<\/jats:sub>\n                      \u2264 1.77\u00a0mg\u00b7h\/L and C\n                      <jats:sub>max, ss<\/jats:sub>\n                      \u2264 140\u00a0\u00b5g\/L). This trend was confirmed by Monte-Carlo simulations in 1,000 virtual patients and suggests TDM when the higher dosage is given.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This PopPK model provides an initial characterisation of rivaroxaban disposition in post-TIPS patients and reveals a markedly reduced apparent V\/F relative to non-TIPS populations. The 5\u00a0mg once-daily regimen is generally safe, while the 10\u00a0mg dose may be considered with therapeutic drug monitoring to account for substantial inter-individual pharmacokinetic variability in post-TIPS patients.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>Chinese Clinical Trial Registry, ChiCTR (ChiCTR2300073784); registered 20 July 2023.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s00228-026-04034-6","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T06:42:51Z","timestamp":1774334571000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population pharmacokinetics of rivaroxaban after transjugular intrahepatic portosystemic shunt"],"prefix":"10.1007","volume":"82","author":[{"given":"Min","family":"Jia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming","family":"Chai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changyou","family":"Jing","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunlei","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aili","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanqiu","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingmei","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"issue":"6","key":"4034_CR1","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1007\/s00228-024-03648-y","volume":"80","author":"MME Diesveld","year":"2024","unstructured":"Diesveld MME, Pijnenburg DWMJ, Weersink RA, Barzel I, Drenth JPH, Lisman T et al (2024) Recommendations for the safe use of direct oral anticoagulants in patients with cirrhosis based on a systematic review of pharmacokinetic, pharmacodynamic and safety data. 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