{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T04:47:27Z","timestamp":1793767647568,"version":"4.6.1"},"reference-count":47,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T00:00:00Z","timestamp":1670544000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:sec>\n                    <jats:title>Aim<\/jats:title>\n                    <jats:p>Alemtuzumab is a monoclonal antibody used as induction immunosuppressive therapy in kidney transplantation. It targets CD52 on lymphocytes, inducing profound immune cell depletion upon administration. Owing to its off\u2010label status in kidney transplantation, its pharmacokinetic characteristics are largely unknown in this setting, and its current fixed dosing algorithm originates from other populations. We developed a population pharmacokinetic model for alemtuzumab in kidney transplant recipients and investigated the potential of personalized alemtuzumab therapy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In total, 362 pharmacokinetic observations drawn 0\u2010165\u2009days after transplantation were available from 61 adult kidney transplant recipients who received two consecutive doses of 15\u2009mg alemtuzumab subcutaneously. A population pharmacokinetic model was developed using nonlinear mixed\u2010effects modelling and applied to simulate various dosing regimens.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The alemtuzumab concentration\u2010time data were best described by a two\u2010compartmental model with first\u2010order absorption and parallel first\u2010order and time\u2010varying concentration\u2010dependent elimination, with between\u2010subject variability on the first\u2010order elimination (39.6%) and central distribution volume (39.6%). Alemtuzumab pharmacokinetics varied with body size, rendering lighter individuals exposed to lympholytic alemtuzumab concentrations (&gt;0.1\u00a0mg\/L) for prolonged durations as compared to their heavier peers. This between\u2010subject variability could be reduced through lean bodyweight\u2010adjusted dosing, showing a twofold to threefold reduction in the slope of the median alemtuzumab exposure over the bodyweight range.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Alemtuzumab displays substantial pharmacokinetic variability in kidney transplant recipients, which may warrant a personalized treatment strategy. Lean bodyweight\u2010adjusted dosing poses an option for individualized dosing, but further evaluation of its potential clinical benefit is warranted.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bcp.15608","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T05:26:19Z","timestamp":1669008379000},"page":"1471-1485","source":"Crossref","is-referenced-by-count":10,"title":["Population pharmacokinetics of subcutaneous alemtuzumab in kidney transplantation"],"prefix":"10.1111","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3692-0901","authenticated-orcid":false,"given":"Tom C.","family":"Zwart","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Toxicology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Bezstarosti","sequence":"additional","affiliation":[{"name":"Department of Immunology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica R.","family":"Achini","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlies E. J.","family":"Reinders","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Nephrology) and LUMC Transplant Center Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco W.","family":"Schilham","sequence":"additional","affiliation":[{"name":"Department of Paediatrics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastiaan","family":"Heidt","sequence":"additional","affiliation":[{"name":"Department of Immunology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk\u2010Jan","family":"Guchelaar","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Toxicology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan W.","family":"de Fijter","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine (Nephrology) and LUMC Transplant Center Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk Jan A. 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