{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T10:49:52Z","timestamp":1762253392360,"version":"3.37.3"},"reference-count":0,"publisher":"Georg Thieme Verlag KG","issue":"05","funder":[{"name":"Dutch Innovation fund"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2020,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>\n          Background\u2003The currently published population pharmacokinetic (PK) models used for PK-guided dosing in hemophilia patients are based on clinical trial data and usually not externally validated in clinical practice. The aim of this study was to validate a published model for recombinant factor VIII-Fc fusion protein (rFVIII-Fc) concentrate and to develop an enriched model using independently collected clinical data if required.<\/jats:p><jats:p>\n          Methods\u2003Clinical data from hemophilia A patients treated with rFVIII-Fc concentrate (Elocta) participating in the United Kingdom Extended Half-Life Outcomes Registry were collected. The predictive performance of the published model was assessed using mean percentage error (bias) and mean absolute percentage error (inaccuracy). An extended population PK model was developed using nonlinear mixed-effects modeling (NONMEM).<\/jats:p><jats:p>\n          Results\u2003A total of 43 hemophilia A patients (FVIII \u2264 2\u2009IU\/dL), aged 5 to 70 years, were included. The prior model was able to predict the collected 244 rFVIII-Fc levels without significant bias (\u20131.0%, 95% CI: \u20139.4 to 7.3%) and with acceptable accuracy (12.9%). However, clearance and central distribution volume were under predicted in patients &lt;12 years, which was expected as this age group was not represented in the previous model population. An enriched population PK model was constructed, which was able to successfully characterize PK profiles of younger children.<\/jats:p><jats:p>\n          Conclusion\u2003We concluded that the existing rFVIII-Fc population PK model is valid for patients\u2009\u2265\u200912 years. However, it is not reliable in younger patients. Our alternative model, constructed from real world patient data including children, allows for better description of patients \u22655 years.<\/jats:p>","DOI":"10.1055\/s-0040-1709522","type":"journal-article","created":{"date-parts":[[2020,5,5]],"date-time":"2020-05-05T22:37:44Z","timestamp":1588718264000},"page":"747-757","source":"Crossref","is-referenced-by-count":11,"title":["A Novel, Enriched Population Pharmacokinetic Model for Recombinant Factor VIII-Fc Fusion Protein Concentrate in Hemophilia A Patients"],"prefix":"10.1055","volume":"120","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7967-1023","authenticated-orcid":false,"given":"Laura H.","family":"Bukkems","sequence":"additional","affiliation":[{"name":"Hospital Pharmacy-Clinical Pharmacology, Amsterdam University Medical Centers, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica M.","family":"Heijdra","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology, Erasmus University Medical Center \u2013 Sophia Children's Hospital Rotterdam, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary","family":"Mathias","sequence":"additional","affiliation":[{"name":"Haemophilia Comprehensive Care Centre, Great Ormond Street Hospital for Children NHS Foundation Trust, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter W.","family":"Collins","sequence":"additional","affiliation":[{"name":"Arthur Bloom Haemophilia Centre, School of Medicine, Cardiff University Hospital, Cardiff, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles R. M.","family":"Hay","sequence":"additional","affiliation":[{"name":"University Department of Haematology, Manchester University NHS Foundation Trust, Manchester, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert C.","family":"Tait","sequence":"additional","affiliation":[{"name":"Department of Haematology, Royal Infirmary, Glasgow, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Mangles","sequence":"additional","affiliation":[{"name":"Haemophilia, Haemostasis and Thrombosis Centre, Hampshire Hospitals NHS Foundation Trust, Basingstoke, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bethan","family":"Myers","sequence":"additional","affiliation":[{"name":"Department of Haematology, United Lincolnshire Hospitals NHS Trust, Lincoln, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Evans","sequence":"additional","affiliation":[{"name":"Department of Haematology, East Kent Hospitals University NHS Foundation Trust, Kent, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Bailiff","sequence":"additional","affiliation":[{"name":"Department Haematology and Blood Transfusion, University Hospitals Coventry and Warwickshire NHS Trust, Coventry, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicola","family":"Curry","sequence":"additional","affiliation":[{"name":"Oxford Haemophilia and Thrombosis Centre and Oxford NIHR BRC, Churchill Hospital, Oxford, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeanette","family":"Payne","sequence":"additional","affiliation":[{"name":"Department of PaediatricHaematology, Sheffield Children's NHS Foundation Trust, Sheffield, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steve","family":"Austin","sequence":"additional","affiliation":[{"name":"Centre for Haemostasis and Thrombosis, St George's University Hospitals NHS Foundation Trust, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tine M. H. J.","family":"Goedhart","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology, Erasmus University Medical Center \u2013 Sophia Children's Hospital Rotterdam, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Frank W. G.","family":"Leebeek","sequence":"additional","affiliation":[{"name":"Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karina","family":"Meijer","sequence":"additional","affiliation":[{"name":"Department of Hematology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karin","family":"Fijnvandraat","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Amsterdam University Medical Centers, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6690-8586","authenticated-orcid":false,"given":"Pratima","family":"Chowdary","sequence":"additional","affiliation":[{"name":"Katharine DormandyHaemophilia Centre and Thrombosis Unit, Royal Free London NHS Foundation Trust, London, United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ron A. A.","family":"Math\u00f4t","sequence":"additional","affiliation":[{"name":"Hospital Pharmacy-Clinical Pharmacology, Amsterdam University Medical Centers, Amsterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marjon H.","family":"Cnossen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Hematology, Erasmus University Medical Center \u2013 Sophia Children's Hospital Rotterdam, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"for UK-EHL Outcomes Registry OPTI-CLOT Collaboration","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2020,5,5]]},"container-title":["Thrombosis and Haemostasis"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/s-0040-1709522.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,5,5]],"date-time":"2020-05-05T22:37:50Z","timestamp":1588718270000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/s-0040-1709522"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5]]},"references-count":0,"journal-issue":{"issue":"05","published-online":{"date-parts":[[2020,5,5]]},"published-print":{"date-parts":[[2020,5]]}},"URL":"https:\/\/doi.org\/10.1055\/s-0040-1709522","relation":{},"ISSN":["0340-6245","2567-689X"],"issn-type":[{"type":"print","value":"0340-6245"},{"type":"electronic","value":"2567-689X"}],"subject":[],"published":{"date-parts":[[2020,5]]}}}