{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,2]],"date-time":"2026-06-02T09:41:28Z","timestamp":1780393288976,"version":"3.54.1"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T00:00:00Z","timestamp":1708300800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004792","name":"Minist\u00e8re de l'Enseignement Sup\u00e9rieur et de la Recherche","doi-asserted-by":"publisher","award":["LabEx MAbImprove ANR\u201010\u2010LABX\u201053\u201001"],"award-info":[{"award-number":["LabEx MAbImprove ANR\u201010\u2010LABX\u201053\u201001"]}],"id":[{"id":"10.13039\/501100004792","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2024,5]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Eculizumab is a monoclonal antibody targeting complement protein C5 used in renal diseases. As recommended dosing regimen leads to unnecessarily high concentrations in some patients, tailored dosing therapeutic drug monitoring was proposed to reduce treatment cost. The objectives of the present work were (i) to investigate the target\u2010mediated elimination of eculizumab and (ii) whether a pharmacokinetic model integrating a nonlinear elimination allows a better prediction of eculizumab concentrations than a linear model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We analysed 377 eculizumab serum concentrations from 44 patients treated for atypical haemolytic uraemic syndrome and C3 glomerulopathy with a population pharmacokinetic approach. Critical concentrations (below which a non\u2010log\u2010linear decline of concentration over time is evidenced) were computed to estimate the relevance of the target\u2010mediated elimination. Simulations of dosing regimens were then performed to predict probabilities of target attainment (i.e. trough &gt;100\u2009mg\/L).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Pharmacokinetics of eculizumab was nonlinear and followed a mixture of first\u2010order (<jats:italic>CL<\/jats:italic>\u2009=\u20091.318\u2009mL\/day\/kg) and Michaelis\u2013Menten elimination (<jats:italic>V<\/jats:italic><jats:sub>max<\/jats:sub>\u2009=\u200926.07\u2009mg\/day, <jats:italic>K<\/jats:italic><jats:sub>m<\/jats:sub>\u2009=\u200924.06\u2009mg\/L). Volume of distribution (72.39\u2009mL\/kg) and clearance were weight\u2010dependent. Critical concentrations (<jats:italic>V<\/jats:italic><jats:sub>max<\/jats:sub>\/<jats:italic>CL<\/jats:italic>) ranged from 144.7 to 759.7\u00a0mg\/L and were inversely related to body weight (<jats:italic>P<\/jats:italic>\u2009=\u2009.013). Nonlinearity was thus noticeable at therapeutic concentrations. Simulations predicted that 1200\u2009mg of eculizumab every 21\u2009days would allow 85% and 76% of patients to maintain a therapeutic exposure, for 50 or 90\u2009kg body weight, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our study investigates the nonlinear elimination of eculizumab and discusses the importance of accounting for eculizumab target\u2010mediated elimination in therapeutic drug monitoring.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.16019","type":"journal-article","created":{"date-parts":[[2024,2,20]],"date-time":"2024-02-20T02:09:00Z","timestamp":1708394940000},"page":"1312-1321","source":"Crossref","is-referenced-by-count":5,"title":["Eculizumab dose tapering should take into account the nonlinearity of its pharmacokinetics"],"prefix":"10.1111","volume":"90","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9308-4933","authenticated-orcid":false,"given":"Olivier","family":"Le 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French National Institute of Health and Medical Research  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2634-2450","authenticated-orcid":false,"given":"Christophe","family":"Passot","sequence":"additional","affiliation":[{"name":"Integrated Center for Oncology  Angers France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Bertrand","sequence":"additional","affiliation":[{"name":"Nephrology Department and Transplantation Center Rouen University Hospital  Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Desvignes","sequence":"additional","affiliation":[{"name":"Inserm U1327 ISCHEMIA \u201cMembrane signalling and inflammation in reperfusion injuries\u201d Universit\u00e9 de Tours  Tours France"},{"name":"Pilot Centre for Therapeutic Antibodies Monitoring (PiTAM) CHRU Tours  Tours 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