{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T11:22:13Z","timestamp":1781522533460,"version":"3.54.1"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T00:00:00Z","timestamp":1653436800000},"content-version":"vor","delay-in-days":83,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001826","name":"ZonMw","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001826","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Goed Gebruik Geneesmiddelen","award":["836031008"],"award-info":[{"award-number":["836031008"]}]},{"name":"Dutch Board of Health Insurance"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,2,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Eculizumab is a lifesaving yet expensive drug for atypical haemolytic uraemic syndrome (aHUS). Current guidelines advise a fixed-dosing schedule, which can be suboptimal and inflexible in the individual patient.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We evaluated the pharmacokinetics (PK) and pharmacodynamics (PD) [classical pathway (CP) activity levels] of eculizumab in 48 patients, consisting of 849 time-concentration data and 569 CP activity levels. PK\u2013PD modelling was performed with non-linear mixed-effects modelling. The final model was used to develop improved dosing strategies.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>A PK model with parallel linear and non-linear elimination rates best described the data with the parameter estimates clearance 0.163 L\/day, volume of distribution 6.42 L, maximal rate 29.6 mg\/day and concentration for 50% of maximum rate 37.9 mg\/L. The PK\u2013PD relation between eculizumab concentration and CP activity was described using an inhibitory Emax model with the parameter estimates baseline 101%, maximal inhibitory effect 95.9%, concentration for 50% inhibition 22.0 mg\/L and \u00a0Hill\u00a0coefficient\u00a05.42. A weight-based loading dose, followed by PK-guided dosing was found to improve treatment. On day 7, we predict 99.95% of the patients to reach the efficacy target (CP activity\u00a0&amp;lt;10%),\u00a0compared with 94.75% with standard dosing. Comparable efficacy was predicted during the maintenance phase, while the dosing interval could be prolonged in \u223c33% of the population by means of individualized dosing. With a fixed-dose 4-week dosing interval to allow for holidays, treatment costs will increase by 7.1% and we predict 91% of the patients will reach the efficacy target.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>A patient-friendly individualized dosing strategy of eculizumab has the potential to improve treatment response at reduced costs.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ndt\/gfac056","type":"journal-article","created":{"date-parts":[[2022,3,1]],"date-time":"2022-03-01T12:10:43Z","timestamp":1646136643000},"page":"362-371","source":"Crossref","is-referenced-by-count":13,"title":["Proposal for individualized dosing of eculizumab in atypical haemolytic uraemic syndrome: patient friendly and cost-effective"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5757-4919","authenticated-orcid":false,"given":"Mendy","family":"ter Avest","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Radboud Institute for Health Sciences, Radboud University Medical Centre , Nijmegen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romy N","family":"Bouwmeester","sequence":"additional","affiliation":[{"name":"Department of Paediatric Nephrology, Radboud Institute for Molecular Life Sciences, Amalia Children's Hospital, Radboud University Medical Centre , Nijmegen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Duineveld","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Radboud University Medical Centre , Nijmegen , The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kioa L","family":"Wijnsma","sequence":"additional","affiliation":[{"name":"Department of Paediatric Nephrology, Radboud Institute for Molecular Life Sciences, Amalia Children's Hospital, Radboud University 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