{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T12:11:50Z","timestamp":1770898310576,"version":"3.50.1"},"reference-count":50,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T00:00:00Z","timestamp":1765670400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T00:00:00Z","timestamp":1765670400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","award":["NNF23OC0081717"],"award-info":[{"award-number":["NNF23OC0081717"]}],"id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:p>\n                    The pharmacokinetics (PK) of monoclonal antibodies (mAbs) during pregnancy remains poorly characterized, despite active inflammatory bowel diseases (IBD) being the greatest risk factor for adverse pregnancy outcomes. To quantify pregnancy\u2010induced changes, vedolizumab concentrations from 39 pregnant patients on various dosing regimens were analyzed using a sequential albumin\u2010trend\/PK modeling approach, extending a published vedolizumab non\u2010pregnancy model. Albumin trends were first characterized using a polynomial mixed\u2010effect model. Then, individual changes in albumin from their pre\u2010pregnancy concentrations, implemented as time\u2010varying patient\u2010influential factor (covariate) in the PK model, served as potential biomarker of pregnancy\u2010induced plasma volume expansion. The modeling framework allowed model\u2010informed imputation of missing covariate data, extraction of hemodilution effect, and estimation of pre\u2010pregnancy PK parameters. Due to albumin change, the central volume of distribution increased 52.4%, consistent with known gestational plasma volume expansion, while clearance increased to 38.6%. An additional third\u2010trimester effect of gestational age, potentially reflecting transplacental transfer, increased clearance by an additional 33.3 percentage points. These changes led to a 49.5% decline in vedolizumab trough concentrations (\n                    <jats:italic>C<\/jats:italic>\n                    <jats:sub>min<\/jats:sub>\n                    ) by late pregnancy. To maintain efficacious pre\u2010pregnancy exposure (dependent on the individual dosing interval), dosing intervals were gradually shortened for approximately one\u2010third (e.g., to up to 5.6\u2009weeks for pre\u2010pregnancy 8\u2010week regimens). Optimized dosing times were summarized in an easy\u2010to\u2010use nomogram\u2010like plot. This work provides the first population PK model of vedolizumab in pregnancy. By integrating physiologically motivated pregnancy effects, it advanced quantitative understanding of mAbs PK in pregnancy with potential application to other biologics and provides optimized dosing strategies to mitigate risks of adverse pregnancy outcomes.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70145","type":"journal-article","created":{"date-parts":[[2025,12,15]],"date-time":"2025-12-15T07:46:59Z","timestamp":1765784819000},"page":"457-469","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Physiologically Motivated Sequential Population Modeling of Albumin Trends and Vedolizumab Pharmacokinetics for Pregnancy Dosing Regimen Optimization"],"prefix":"10.1002","volume":"119","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-7080-8985","authenticated-orcid":false,"given":"Zrinka","family":"Duvnjak","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy Freie Universit\u00e4t Berlin  Berlin Germany"},{"name":"Graduate Research Training Program PharMetrX  Berlin\/Potsdam Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5485-607X","authenticated-orcid":false,"given":"Robin","family":"Michelet","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy Freie Universit\u00e4t Berlin  Berlin Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3898-4212","authenticated-orcid":false,"given":"Casper","family":"Steenholdt","sequence":"additional","affiliation":[{"name":"Department of Medical Gastroenterology Odense University Hospital  Odense Denmark"},{"name":"Research Unit of Medical Gastroenterology, Department of Clinical Research University of Southern Denmark  Odense Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7069-3863","authenticated-orcid":false,"given":"Ella S.K.","family":"Widigson","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy Freie Universit\u00e4t Berlin  Berlin Germany"},{"name":"Graduate Research Training Program PharMetrX  Berlin\/Potsdam Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7965-399X","authenticated-orcid":false,"given":"C\u00e6cilie","family":"Skej\u00f8","sequence":"additional","affiliation":[{"name":"Department of Hepatology and Gastroenterology Aarhus University Hospital  Aarhus Denmark"},{"name":"Department of Clinical Medicine Health, Aarhus University  Aarhus Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7752-0229","authenticated-orcid":false,"given":"Jo\u00e3o 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