{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T09:51:49Z","timestamp":1791971509591,"version":"4.3.4"},"reference-count":33,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100011022","name":"Vertex Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100011022","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Suzetrigine (VX\u2010548) is a first\u2010in\u2010class, oral, non\u2010opioid, FDA\u2010approved analgesic for the treatment of moderate to severe acute pain. Based on Phase 1 clinical drug\u2013drug interaction (DDI) studies, suzetrigine is a weak\u2010to\u2010moderate cytochrome P450 3A (CYP3A) inducer and thus has the potential to decrease exposure and impact efficacy of CYP3A substrates, such as apixaban and rivaroxaban, which are commonly used as anticoagulants peri\u2010 and post\u2010operatively. Given this, it is important to assess the DDIs of apixaban and rivaroxaban with suzetrigine. Physiologically based pharmacokinetic (PBPK) models are commonly used to assess DDIs mediated through modulation of CYP3A and were used here to quantify the potential effect of co\u2010administration of suzetrigine on apixaban and rivaroxaban PK. The PBPK models were validated using observed data from suzetrigine, apixaban, and rivaroxaban clinical DDI studies. The validated models predict that suzetrigine decreases apixaban AUCinf by 6.1% (90% confidence interval [CI]: 5.7% to 6.4%) and Cmax by 1.8% (90% CI: 1.7% to 1.9%), and rivaroxaban AUCinf by 8.4% (90% CI: 7.2% to 9.6%) and Cmax by 3.5% (90% CI: 3.3% to 3.7%). The predicted small reductions in apixaban and rivaroxaban exposures (AUCinf &lt;10%) are not expected to be clinically relevant since a 20% no\u2010effect boundary is typically used to determine the clinical impact of a DDI. The PBPK model predictions are consistent with the apixaban and rivaroxaban labels, which do not warn against co\u2010administration with weak or moderate CYP3A inducers, such as suzetrigine.<\/jats:p>","DOI":"10.1002\/jcph.70288","type":"journal-article","created":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T07:45:21Z","timestamp":1789803921000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Suzetrigine Is Not Expected to Have Clinically Relevant DDIs with Apixaban and Rivaroxaban Based on PBPK Modeling"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-7698-8201","authenticated-orcid":false,"given":"Guanyu","family":"Wang","sequence":"first","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8055-4828","authenticated-orcid":false,"given":"Elizabeth","family":"Lakota","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6655-766X","authenticated-orcid":false,"given":"Bo","family":"Feng","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Licong","family":"Jiang","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated  San Diego CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guiqing","family":"Liang","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1910-5605","authenticated-orcid":false,"given":"Brian","family":"Hare","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated  Boston MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,19]]},"reference":[{"issue":"6","key":"e_1_2_11_2_1","first-page":"1085","article-title":"Suzetrigine, a nonopioid NaV1.8 inhibitor for treatment of moderate\u2010to\u2010severe acute pain: two phase 3 randomized clinical trials","volume":"142","author":"Bertoch T","year":"2025","journal-title":"Anesthesiology"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2209870"},{"key":"e_1_2_11_4_1","unstructured":"JOURNAVX prescribing information.Vertex Pharmaceuticals Incorporated; revised January 2025."},{"key":"e_1_2_11_5_1","unstructured":"United States Department of Health and Human Services. Center for Drug Evaluation and Research (CDER). Division of Anesthesiology Addiction Medicine and Pain Medicine (DAAP). Integrated review: application number 219209Orig1s000 (JOURNAVX).Food and Drug Administration. January 30 2025."},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.18636"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2023.2287472"},{"key":"e_1_2_11_8_1","volume-title":"ELIQUIS prescribing information"},{"key":"e_1_2_11_9_1","volume-title":"XARELTO prescribing information","year":"2026"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2503"},{"issue":"1","key":"e_1_2_11_11_1","first-page":"S120","article-title":"Physiologically based pharmacokinetic model\u2010informed drug development for polatuzumab vedotin: label for drug\u2010drug interactions without dedicated clinical trials","volume":"60","author":"Samineni D","year":"2020","journal-title":"J Clin Pharmacol"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/psp4.12619"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-020-04148-3"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.1747"},{"key":"e_1_2_11_15_1","unstructured":"Certara Inc.Simcyp PBPK Simulator (Version 22). 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