{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T05:12:36Z","timestamp":1773810756455,"version":"3.50.1"},"reference-count":16,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T00:00:00Z","timestamp":1772841600000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CPT Pharmacom &amp;amp; Syst Pharma"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Vixarelimab is a first\u2010in\u2010class fully human monoclonal antibody targeting oncostatin M (OSM) receptor beta (OSMR\u03b2). It has been evaluated in Phase 1 and 2 studies in healthy volunteers and patients with chronic pruritic conditions and demonstrated anti\u2010pruritic efficacy in a Phase 2 study in prurigo nodularis, but detailed pharmacokinetic analysis has not been previously reported. In this study, a population pharmacokinetic analysis was performed to characterize the pharmacokinetics of vixarelimab and identify covariates affecting exposure. The analysis dataset contained 4032 measurements from 274 participants from three Phase 1 and 2 studies. A two\u2010compartment target\u2010mediated drug disposition (TMDD) model with a quasi\u2010steady\u2010state (QSS) approximation satisfactorily described the observed concentration\u2010time data across studies and various dose levels. The model estimated linear clearance (CL), central volume (\n                    <jats:italic>V<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>c<\/jats:italic>\n                    <\/jats:sub>\n                    ), and peripheral volume (\n                    <jats:italic>V<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>p<\/jats:italic>\n                    <\/jats:sub>\n                    ) at 0.00649\u2009L\/h, 3.04\u2009L, and 1.74\u2009L, respectively, in line with values for a typical monoclonal antibody. Subcutaneous bioavailability and the absorption rate constant were estimated to be 56.6% and 0.0126\u2009h\n                    <jats:sup>\u22121<\/jats:sup>\n                    , respectively. Body weight was identified as the only statistically significant covariate, positively correlating with CL,\n                    <jats:italic>V<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>c<\/jats:italic>\n                    <\/jats:sub>\n                    , and\n                    <jats:italic>V<\/jats:italic>\n                    <jats:sub>\n                      <jats:italic>p<\/jats:italic>\n                    <\/jats:sub>\n                    . Model\u2010based simulations showed that the clinical impact of body weight on vixarelimab exposure was minor, suggesting that dose adjustment based on weight is not warranted. The developed model provides a thorough understanding of vixarelimab pharmacokinetics and the impact of covariates on exposure to support future clinical development.\n                  <\/jats:p>","DOI":"10.1002\/psp4.70230","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T17:34:26Z","timestamp":1772991266000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population Pharmacokinetic Analysis of Vixarelimab in Healthy Volunteers and Patients With Chronic Pruritic Conditions"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4517-7569","authenticated-orcid":false,"given":"Fei","family":"Tang","sequence":"first","affiliation":[{"name":"Genentech Inc.  South San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve","family":"Dang","sequence":"additional","affiliation":[{"name":"Genentech Inc.  South San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Audrey","family":"Arjomandi","sequence":"additional","affiliation":[{"name":"Genentech Inc.  South San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Pan","sequence":"additional","affiliation":[{"name":"Genentech Inc.  South San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joy","family":"Hsu","sequence":"additional","affiliation":[{"name":"Genentech Inc.  South San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Smita","family":"Kshirsagar","sequence":"additional","affiliation":[{"name":"Genentech Inc.  South San Francisco California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6193-2993","authenticated-orcid":false,"given":"Nastya","family":"Kassir","sequence":"additional","affiliation":[{"name":"Genentech Inc.  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