{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T04:14:34Z","timestamp":1790396074669,"version":"4.1.0"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T00:00:00Z","timestamp":1607299200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100004792","name":"Minist\u00e8re de l'Enseignement Sup\u00e9rieur et de la Recherche","doi-asserted-by":"publisher","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":[[2021,5]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Eculizumab is an anti\u2010C5 monoclonal antibody approved for rare diseases including atypical haemolytic\u2013uraemic syndrome. The maintenance phase dosing regimen is identical for all adult patients: 1200 mg every 2 weeks. Recent studies reported an overexposure in many patients when considering a target trough concentration range of 50\u2013100 mg\/L. The aim of the present work was to validate the feasibility of therapeutic drug monitoring of eculizumab in atypical haemolytic\u2013uraemic syndrome patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We performed a 2\u2010step prospective multicentre study. In the first phase, we developed a pharmacokinetic population model using data from 40 patients and identified patients for whom a 1\u2010week lengthening of interval between infusions would lead to a trough concentration above 100 mg\/L. In the second phase, selected patients were allocated a 1\u2010week extension and eculizumab trough concentrations were monitored.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The model confirmed the previously reported influence of bodyweight on elimination clearance and predicted that 36 (90%) patients would be eligible for interval extension. In the second phase of the study, a 1\u2010week lengthening of interval between infusions was performed in 15 patients whose trough concentration at the next visit was predicted with a Bayesian model to be above 100 mg\/L. After interval extension, 10 patients (67%) presented measured trough concentrations over 100 mg\/L. No biological or clinical recurrence of disease was observed, even in the 5 patients with concentrations below 100 mg\/L in whom the initial dosing regimen was resumed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Safe eculizumab interval adjustment is feasible with a PK monitoring.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.14627","type":"journal-article","created":{"date-parts":[[2020,10,29]],"date-time":"2020-10-29T03:15:07Z","timestamp":1603941307000},"page":"2236-2246","source":"Crossref","is-referenced-by-count":12,"title":["Feasibility and safety of tailored dosing schedule for eculizumab based on therapeutic drug monitoring: Lessons from a prospective multicentric study"],"prefix":"10.1111","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2634-2450","authenticated-orcid":false,"given":"Christophe","family":"Passot","sequence":"first","affiliation":[{"name":"EA7501 University of Tours  France"},{"name":"Laboratory of Pharmacology\u2010Toxicology CHRU de Tours  France"},{"name":"Integrated Center for Oncology  Angers France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Sberro\u2010Soussan","sequence":"additional","affiliation":[{"name":"Service de N\u00e9phrologie et Transplantation Adulte, H\u00f4pital Necker\u2010Enfants Malades Universit\u00e9 Paris Descartes, Assistance Publique\u2010H\u00f4pitaux de Paris  Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Bertrand","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Transplantation Centre  Rouen France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Caillard","sequence":"additional","affiliation":[{"name":"Nephrology and Transplant Department Strasbourg University Hospital  Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Betoul","family":"Schvartz","sequence":"additional","affiliation":[{"name":"Nephrology and Transplant Department  Reims France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Domenger","sequence":"additional","affiliation":[{"name":"Nephrology and Transplant Department  Grenoble France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9cile","family":"Contin\u2010Bordes","sequence":"additional","affiliation":[{"name":"Laboratory of Immunology and Immunogenetic  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilles","family":"Paintaud","sequence":"additional","affiliation":[{"name":"EA7501 University of Tours  France"},{"name":"Laboratory of Pharmacology\u2010Toxicology CHRU de Tours  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean\u2010Michel","family":"Halimi","sequence":"additional","affiliation":[{"name":"EA4245 Transplant Immunology and Inflammation Universit\u00e9 de Tours  Tours France"},{"name":"Service de N\u00e9phrologie\u2010Hypertension art\u00e9rielle, Dialyses, Transplantation r\u00e9nale CHRU Tours  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Ternant","sequence":"additional","affiliation":[{"name":"EA7501 University of Tours  France"},{"name":"Laboratory of Pharmacology\u2010Toxicology CHRU de Tours  France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1664-2879","authenticated-orcid":false,"given":"Philippe","family":"Gatault","sequence":"additional","affiliation":[{"name":"EA4245 Transplant Immunology and Inflammation Universit\u00e9 de Tours  Tours France"},{"name":"Service de N\u00e9phrologie\u2010Hypertension art\u00e9rielle, Dialyses, Transplantation r\u00e9nale CHRU Tours  France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,12,7]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1600280"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0161-5890(96)00078-8"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1344"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-03-637645"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa061648"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1208981"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(17)30369-1"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(13)70076-0"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(18)30114-5"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.ajkd.2017.11.019"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/ajt.15364"},{"key":"e_1_2_12_13_1","unstructured":"Editor MBH.Health chiefs refuse to pay for lifesaving kidney treatment. 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