{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T00:38:47Z","timestamp":1781311127290,"version":"3.54.1"},"reference-count":45,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T00:00:00Z","timestamp":1747267200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:p>Alemtuzumab is a T cell\u2010depleting monoclonal antibody that is used for the prevention of kidney transplant rejection. The duration of lymphodepletion after the current standard induction therapy dose is likely longer than necessary, resulting in prolonged T cell lymphopenia with the associated risk of infections. Here, the interplay between alemtuzumab exposure and T cell dynamics was quantitatively evaluated, and the influence of different doses on T cell recovery was investigated. A population pharmacokinetic\u2010pharmacodynamic model describing the interplay between 30\u2009mg alemtuzumab induction therapy and T cell dynamics in kidney transplantation was developed using NONMEM, using pharmacodynamic data from the Triton study (NCT02057965). The developed model was used to perform an exposure\u2010response analysis and investigate dose optimization with model\u2010derived simulations. In total, 418 peripheral blood T cell measurements from 61 adult kidney transplant recipients were included for model development. A single\u2010compartment turnover <jats:italic>E<\/jats:italic><jats:sub>max<\/jats:sub> model with a first\u2010order T cell influx with feedback and a first\u2010order T cell efflux with parallel alemtuzumab\u2010stimulated T cell removal best described the data. Higher alemtuzumab exposure was associated with lower individual\u2010predicted T cells 4\u2009weeks after administration and longer T cell recovery (&gt;\u2009200 cells\/\u03bcL). In the simulations, a fixed dose of 15\u2009mg improved median recovery times by 19\u2009days as compared to the standard 30\u2009mg dose without influencing early T cell depletion. A population pharmacokinetic\u2010pharmacodynamic model adequately described T cell dynamics after alemtuzumab induction therapy in kidney transplant recipients. This model can be used to inform future dose\u2010optimization studies of alemtuzumab in different clinical settings.<\/jats:p>","DOI":"10.1002\/cpt.3714","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T23:05:51Z","timestamp":1747350351000},"page":"662-672","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Alemtuzumab Exposure and T Lymphocyte Depletion: A Population Pharmacokinetic\u2010Pharmacodynamic Model of Alemtuzumab Induction Therapy for Kidney Transplantation"],"prefix":"10.1002","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7343-0130","authenticated-orcid":false,"given":"Lukas K.","family":"van Vugt","sequence":"first","affiliation":[{"name":"Erasmus MC Transplant Institute  Rotterdam The Netherlands"},{"name":"Division of Nephrology and Transplantation, Department of Internal Medicine Erasmus MC, University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3692-0901","authenticated-orcid":false,"given":"Tom C.","family":"Zwart","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Toxicology Leiden University Medical Center  Leiden The Netherlands"},{"name":"Department of Hospital Pharmacy Haga Teaching Hospital  The Hague The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0315-115X","authenticated-orcid":false,"given":"Suzanne","family":"Bezstarosti","sequence":"additional","affiliation":[{"name":"Department of Immunology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6700-188X","authenticated-orcid":false,"given":"Sebastiaan","family":"Heidt","sequence":"additional","affiliation":[{"name":"Erasmus MC Transplant Institute  Rotterdam The Netherlands"},{"name":"Division of Nephrology and Transplantation, Department of Internal Medicine Erasmus MC, University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9543-567X","authenticated-orcid":false,"given":"Marlies E. 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