{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T14:38:17Z","timestamp":1784039897176,"version":"3.55.0"},"reference-count":39,"publisher":"BMJ","issue":"7","license":[{"start":{"date-parts":[[2025,7,4]],"date-time":"2025-07-04T00:00:00Z","timestamp":1751587200000},"content-version":"unspecified","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,6,6]]},"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>To predict the level at a specified time and design personalised dosing, we proposed a method (Method 1) for estimating coagulation factor VIII (FVIII) pharmacokinetic (PK) parameters using 4 levels within 48 hours after administering a test dose.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>A retrospective study based on virtual populations and real patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Setting<\/jats:title>\n                  <jats:p>A comprehensive hospital in China.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Participants<\/jats:title>\n                  <jats:p>Virtual populations generated by Monte Carlo simulations and retrospectively collected real patient data.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>PK profiles of FVIII after dosing in the virtual populations were generated from a published population PK model coupled with Monte Carlo simulation. The simulated coagulation factor levels were considered as the reference (C<jats:sub>ref<\/jats:sub>). FVIII levels at six sampling points after dosing were estimated with Method 1 and the method proposed by Lisheng Cai (Method 2) and compared with C<jats:sub>ref<\/jats:sub>. PK data from three patients with severe haemophilia A were retrospectively collected to further validate the accuracy of the two methods.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In the adult group, the maximum mean deviations for Methods 1 and 2 were 0.43% (\u00b10.35%) and \u221236.31% (\u00b16.67%), with corresponding maximum root mean square errors (RMSE) of 0.12% and 28.44%, respectively. For the paediatric group, the maximum mean deviations for Methods 1 and 2 were 0.13% (\u00b10.25%) and \u221234.27% (\u00b16.74%), with maximum RMSEs of 0.05% and 25.33%, respectively. In three actual patients, mean deviations using Method 1 were 0.32%, 1.34% and 0.24%. Mean deviations using Method 2 were 13.37%, \u221216.86% and 56.66%.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>The proposed method for estimating FVIII PK parameters and levels demonstrates high accuracy and has the potential for precision dosing.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2024-097053","type":"journal-article","created":{"date-parts":[[2025,7,5]],"date-time":"2025-07-05T09:45:30Z","timestamp":1751708730000},"page":"e097053","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":1,"title":["Development and validation of an innovative approach to estimating FVIII levels and designing personalised doses in the prophylactic treatment of haemophilia A: based on the principle of the two-compartment model"],"prefix":"10.1136","volume":"15","author":[{"given":"Zipeng","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, China"},{"name":"School of Pharmacy, Fujian Medical University, Fuzhou, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianxing","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, China"},{"name":"School of Pharmacy, Fujian Medical University, Fuzhou, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baohua","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, China"},{"name":"School of Pharmacy, Fujian Medical University, Fuzhou, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, China"},{"name":"School of Pharmacy, Fujian Medical University, Fuzhou, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingxia","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, China"},{"name":"School of Pharmacy, Fujian Medical University, Fuzhou, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuxia","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maobai","family":"Liu,","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meijuan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenge","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Hematology, Fujian Medical University Union Hospital, Fuzhou, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1640-7385","authenticated-orcid":false,"given":"Xuemei","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Fujian Medical University Union Hospital, Fuzhou, Fujian, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2025,7,5]]},"reference":[{"key":"2025080306100811000_15.7.e097053.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)13405-8"},{"key":"2025080306100811000_15.7.e097053.2","doi-asserted-by":"crossref","first-page":"2012","DOI":"10.1111\/jth.15803","article-title":"A personalized limited sampling approach to better estimate terminal half-life of FVIII concentrates","volume":"20","author":"Chelle","year":"2022","journal-title":"J Thromb Haemost"},{"key":"2025080306100811000_15.7.e097053.3","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa067659"},{"key":"2025080306100811000_15.7.e097053.4","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2011.04214.x"},{"key":"2025080306100811000_15.7.e097053.5","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1046\/j.1365-2516.9.s1.4.x","article-title":"Prophylactic dosing of factor VIII and factor IX from a clinical pharmacokinetic perspective","volume":"9 Suppl 1","author":"Bj\u00f6rkman","year":"2003","journal-title":"Haemophilia"},{"key":"2025080306100811000_15.7.e097053.6","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2009.03703.x"},{"key":"2025080306100811000_15.7.e097053.7","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1053\/j.seminhematol.2015.10.006","article-title":"Factor VIII\/factor IX prophylaxis for severe hemophilia","volume":"53","author":"Carcao","year":"2016","journal-title":"Semin Hematol"},{"key":"2025080306100811000_15.7.e097053.8","first-page":"1","article-title":"The pharmacokinetics of coagulation factors","volume":"12 Suppl 3","author":"Lee","year":"2006","journal-title":"Haemophilia"},{"key":"2025080306100811000_15.7.e097053.9","doi-asserted-by":"crossref","first-page":"1313","DOI":"10.1080\/17425255.2016.1214711","article-title":"The use of pharmacokinetics in dose individualization of factor VIII in the treatment of hemophilia A","volume":"12","author":"McEneny-King","year":"2016","journal-title":"Expert Opin Drug Metab Toxicol"},{"key":"2025080306100811000_15.7.e097053.10","doi-asserted-by":"publisher","DOI":"10.1111\/hae.12094"},{"key":"2025080306100811000_15.7.e097053.11","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/ejh.12370","article-title":"Methods for individualising factor VIII dosing in prophylaxis","volume":"76","author":"Ar","year":"2014","journal-title":"Eur J Haematol Suppl"},{"key":"2025080306100811000_15.7.e097053.12","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1111\/j.1600-0609.1993.tb00638.x","article-title":"Pharmacokinetic dosing in prophylactic treatment of hemophilia A","volume":"51","author":"Carlsson","year":"1993","journal-title":"Eur J Haematol"},{"key":"2025080306100811000_15.7.e097053.13","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200140110-00003"},{"key":"2025080306100811000_15.7.e097053.14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2005.01149.x"},{"key":"2025080306100811000_15.7.e097053.15","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1111\/jth.13867","article-title":"Estimating and interpreting the pharmacokinetic profiles of individual patients with hemophilia A or B using a population pharmacokinetic approach: communication from the SSC of the ISTH","volume":"15","author":"Iorio","year":"2017","journal-title":"J Thromb Haemost"},{"key":"2025080306100811000_15.7.e097053.16","doi-asserted-by":"crossref","DOI":"10.2196\/resprot.6558","article-title":"Development of a Web-Accessible Population Pharmacokinetic Service-Hemophilia (WAPPS-Hemo): Study Protocol","volume":"5","author":"Iorio","year":"2016","journal-title":"JMIR Res Protoc"},{"key":"2025080306100811000_15.7.e097053.17","doi-asserted-by":"crossref","first-page":"e50","DOI":"10.1111\/hae.13141","article-title":"Experience of tailoring prophylaxis using factor VIII pharmacokinetic parameters estimated with myPKFiT\u00ae in patients with severe haemophilia A without inhibitors","volume":"23","author":"\u00c1lvarez-Rom\u00e1n","year":"2017","journal-title":"Haemophilia"},{"key":"2025080306100811000_15.7.e097053.18","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1111\/hae.14295","article-title":"A comparison of MyPKFiT and WAPPS-Hemo as dosing tools for optimizing prophylaxis in patients with severe haemophilia A treated with Octocog alfa","volume":"27","author":"Arvanitakis","year":"2021","journal-title":"Haemophilia"},{"key":"2025080306100811000_15.7.e097053.19","first-page":"143","article-title":"Study And Application of Pharmacokinetics Mathematical Model of FVIII in hemophilia A","volume":"38","author":"Lisheng","year":"2019","journal-title":"Gansu Medicine"},{"key":"2025080306100811000_15.7.e097053.20","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1046\/j.1351-8216.2002.00136.x","article-title":"Comparative pharmacokinetic studies in haemophilia","volume":"8 Suppl 2","author":"Morfini","year":"2002","journal-title":"Haemophilia"},{"key":"2025080306100811000_15.7.e097053.21","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1055\/s-0038-1623531","article-title":"Cross-evaluation of Pharmacokinetic-Guided Dosing Tools for Factor VIII","volume":"118","author":"Preijers","year":"2018","journal-title":"Thromb Haemost"},{"key":"2025080306100811000_15.7.e097053.22","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-07-360594"},{"key":"2025080306100811000_15.7.e097053.23","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e3180311384"},{"key":"2025080306100811000_15.7.e097053.24","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-009-0676-x"},{"key":"2025080306100811000_15.7.e097053.25","first-page":"109","article-title":"Population pharmacokinetics of continuous infusion of factor VIII in hemophilia-a patients undergoing orthopedic surgery","volume":"7","author":"Bolon-Larger","year":"2015","journal-title":"International Journal of Pharmacy and Pharmaceutical Sciences"},{"key":"2025080306100811000_15.7.e097053.26","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2015.136275"},{"key":"2025080306100811000_15.7.e097053.27","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1002\/cpt.716","article-title":"Elucidation of Factor VIII Activity Pharmacokinetics: A Pooled Population Analysis in Patients With Hemophilia A Treated With Moroctocog Alfa","volume":"102","author":"Abrantes","year":"2017","journal-title":"Clin Pharmacol Ther"},{"key":"2025080306100811000_15.7.e097053.28","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1111\/hae.13192","article-title":"Population pharmacokinetic characterization of BAY 81-8973, a full-length recombinant factor VIII: lessons learned - importance of including samples with factor VIII levels below the quantitation limit","volume":"23","author":"Garmann","year":"2017","journal-title":"Haemophilia"},{"key":"2025080306100811000_15.7.e097053.29","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1007\/s10928-019-09637-4","article-title":"Routine clinical care data for population pharmacokinetic modeling: the case for Fanhdi\/Alphanate in hemophilia A patients","volume":"46","author":"Chelle","year":"2019","journal-title":"J Pharmacokinet Pharmacodyn"},{"key":"2025080306100811000_15.7.e097053.30","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1111\/bcp.13858","article-title":"Dose tailoring of human cell line-derived recombinant factor VIII simoctocog alfa: Using a limited sampling strategy in patients with severe haemophilia A","volume":"85","author":"Delavenne","year":"2019","journal-title":"Br J Clin Pharmacol"},{"key":"2025080306100811000_15.7.e097053.31","doi-asserted-by":"crossref","first-page":"411","DOI":"10.1007\/s10928-019-09634-7","article-title":"Development and evaluation of a generic population pharmacokinetic model for standard half-life factor VIII for use in dose individualization","volume":"46","author":"McEneny-King","year":"2019","journal-title":"J Pharmacokinet Pharmacodyn"},{"key":"2025080306100811000_15.7.e097053.32","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2019.217133"},{"key":"2025080306100811000_15.7.e097053.33","doi-asserted-by":"crossref","DOI":"10.3390\/pharmaceutics12040380","article-title":"Real Life Population Pharmacokinetics Modelling of Eight Factors VIII in Patients with Severe Haemophilia A: Is It Always Relevant to Switch to an Extended Half-Life?","volume":"12","author":"Allard","year":"2020","journal-title":"Pharmaceutics"},{"key":"2025080306100811000_15.7.e097053.34","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1007\/s40262-019-00809-6","article-title":"Development and Validation of a Population-Pharmacokinetic Model for Rurioctacog Alfa Pegol (Adynovate\u00ae): A Report on Behalf of the WAPPS-Hemo Investigators Ad Hoc Subgroup","volume":"59","author":"Chelle","year":"2020","journal-title":"Clin Pharmacokinet"},{"key":"2025080306100811000_15.7.e097053.35","doi-asserted-by":"crossref","first-page":"1902","DOI":"10.3324\/haematol.2019.241554","article-title":"Factor VIII activity and bleeding risk during prophylaxis for severe hemophilia A: a population pharmacokinetic model","volume":"106","author":"Tiede","year":"2021","journal-title":"Haematologica"},{"key":"2025080306100811000_15.7.e097053.36","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1111\/hae.14493","article-title":"Influence of blood group and von Willebrand factor on population pharmacokinetics and dose individualization of recombinant factor VIII in Taiwanese patients with haemophilia A","volume":"28","author":"Singkham","year":"2022","journal-title":"Haemophilia"},{"key":"2025080306100811000_15.7.e097053.37","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-009-0699-3"},{"key":"2025080306100811000_15.7.e097053.38","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1111\/jth.12816","article-title":"The pharmacokinetics of a B-domain truncated recombinant factor VIII, turoctocog alfa (NovoEight\u00ae), in patients with hemophilia A","volume":"13","author":"Jim\u00e9nez-Yuste","year":"2015","journal-title":"J Thromb Haemost"},{"key":"2025080306100811000_15.7.e097053.39","doi-asserted-by":"crossref","first-page":"1288","DOI":"10.1111\/jth.14473","article-title":"Functional polymorphisms in the LDLR and pharmacokinetics of Factor VIII concentrates","volume":"17","author":"Lunghi","year":"2019","journal-title":"J Thromb Haemost"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2024-097053","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,3]],"date-time":"2025-08-03T13:10:24Z","timestamp":1754226624000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2024-097053"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":39,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7,5]]},"published-print":{"date-parts":[[2025,7]]}},"alternative-id":["10.1136\/bmjopen-2024-097053"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2024-097053","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7]]}}}