{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:20:44Z","timestamp":1760145644292,"version":"build-2065373602"},"reference-count":32,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T00:00:00Z","timestamp":1724371200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"AICE"},{"name":"Italian PRIN project"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background\/Objectives: A compartmental pharmacokinetics (PK) analysis of new extended half-life FVIII concentrates has never been performed in a large cohort of hemophilia patients. An improved PK analysis of individual outcomes may help to tailor hemophilia replacement treatment. Methods: PK outcomes after the infusion of a standard single dose of Efmoroctocog alfa were collected from 173 patients with severe\/moderately severe hemophilia A in 11 Italian hemophilia centers. Factor VIII clotting activity (FVIII:C) was measured by one-stage clotting assay (OSA) in all patients, and chromogenic substrate assay (CSA) in a subgroup (n = 52). Fifty patients underwent a comparative PK assessment with standard half-life (SHL) recombinant FVIII (rFVIII) products. Non-compartmental analysis (NCA), one compartment model (OCM), and TCM were used to analyze the decay curves of all patients, and one-way paired ANOVA to compare the PK outcomes. Results: All 173 PKs conformed to the NCA and OCM, but only 106 (61%) conformed to the TCM based on the biphasic features of their decay curves. According to the TCM, the Beta HL and MRT of rFVIIIFc were 20.42 \u00b1 7.73 and 25.64 \u00b1 7.61 h, respectively. ANOVA analysis of the outcomes from the three PK models showed significant differences in clearance, half-life (HL), and mean residence time (MRT) (p &lt; 0.001 for all parameters). As anticipated, the HL and MRT of rFVIIIFc were longer than those of SHL rFVIII. Comparing OSA with CSA outcomes, Cmax resulted higher when measured by CSA (p = 0.05) and, according to TCM, Beta HL resulted longer when measured by OSA (p = 0.03). FVIII:C trough levels obtained with SHL concentrates were significantly lower than those obtained with rFVIIIFc at each post-infusion time point. Conclusions: In a large group of hemophilia A (HA) patients, three different PK models confirmed the improved pharmacokinetic (PK) characteristics of rFVIIIFc, compared with standard half-life rFVIII concentrates. The TCM only fits two-thirds of the PKs, highlighting their biphasic decay and a long Beta half-life. In these patients, the TCM would be preferable to properly evaluate individual PK features.<\/jats:p>","DOI":"10.3390\/jcm13174986","type":"journal-article","created":{"date-parts":[[2024,8,23]],"date-time":"2024-08-23T12:53:19Z","timestamp":1724417599000},"page":"4986","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacokinetics of Efmoroctocog alfa by Two-Compartment Model Highlights Hemophilia A Patients with Biphasic Decay, Long Mean Residence Time, and Beta Half-Life"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6565-4943","authenticated-orcid":false,"given":"Massimo","family":"Morfini","sequence":"first","affiliation":[{"name":"Italian Association of Hemophilia Centers (AICE), I 20120 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7423-9864","authenticated-orcid":false,"given":"Flora","family":"Peyvandi","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, University of Milan, Fondazione IRCSS Ca\u2019 Granda Maggiore Hospital, \u201cAngelo Bianchi Bonomi\u201d, I 20120 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7113-4028","authenticated-orcid":false,"given":"Maria Elisa","family":"Mancuso","sequence":"additional","affiliation":[{"name":"Center for Thrombosis and Hemorrhagic Diseases, IRCCS \u201c Humanitas Research Hospital\u201d, Rozzano, I 20142 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Emanuela","family":"Marchesini","sequence":"additional","affiliation":[{"name":"Hemophilia Centre, Internal and Cardiovascular Medicine, \u201cSanta Maria della Misericordia\u201d University Hospital, I 06100 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3529-6334","authenticated-orcid":false,"given":"Annarita","family":"Tagliaferri","sequence":"additional","affiliation":[{"name":"Regional Reference Centre for Inherited Bleeding Disorders, University Hospital of Parma, I 43100 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6465-7624","authenticated-orcid":false,"given":"Roberta","family":"Gualtierotti","sequence":"additional","affiliation":[{"name":"Department of Pathophysiology and Transplantation, University of Milan, Fondazione IRCSS Ca\u2019 Granda Maggiore Hospital, \u201cAngelo Bianchi Bonomi\u201d, I 20120 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4973-1317","authenticated-orcid":false,"given":"Giancarlo","family":"Castaman","sequence":"additional","affiliation":[{"name":"Department of Oncology, Centre for Bleeding Disorders and Coagulation, Careggi University Hospital, I 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Berardino","family":"Pollio","sequence":"additional","affiliation":[{"name":"Regional Reference Centre for Inherited Bleeding and Thrombotic Disorders, Transfusion Medicine, \u201cRegina Margherita\u201d Children Hospital, I 10100 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cristina","family":"Santoro","sequence":"additional","affiliation":[{"name":"Department of Hematology, University Hospital Policlinico \u201cUmberto I\u201d, I 00100 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luisa","family":"Banov","sequence":"additional","affiliation":[{"name":"Regional Reference Centre for Hemorrhagic Diseases, IRCCS Istituto \u201cGiannina Gaslini\u201d, I 16100 Genoa, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8934-2936","authenticated-orcid":false,"given":"Mariasanta","family":"Napolitano","sequence":"additional","affiliation":[{"name":"Hematology Unit, Thrombosis and Hemostasis Reference Regional Centre, University of Palermo, I 90100 Palermo, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paola Stefania","family":"Preti","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Therapeutics, University of Pavia, I 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5081-8201","authenticated-orcid":false,"given":"Rita Carlotta","family":"Santoro","sequence":"additional","affiliation":[{"name":"Regional Reference Centre for Hemophilia and Coagulation Diseases, Azienda Ospedaliera Pugliese \u201cCiaccio\u201d, I 88100 Catanzaro, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3697-706X","authenticated-orcid":false,"given":"Antonio","family":"Coppola","sequence":"additional","affiliation":[{"name":"Regional Reference Centre for Inherited Bleeding Disorders, University Hospital of Parma, I 43100 Parma, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5849-7377","authenticated-orcid":false,"given":"Silvia","family":"Linari","sequence":"additional","affiliation":[{"name":"Department of Oncology, Centre for Bleeding Disorders and Coagulation, Careggi University Hospital, I 50139 Florence, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena","family":"Santagostino","sequence":"additional","affiliation":[{"name":"SOBI, SE-11276 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0305-2212","authenticated-orcid":false,"given":"Francesco","family":"Bernardi","sequence":"additional","affiliation":[{"name":"Department of Life Sciences and Biotechnology, Section of Biochemistry and Molecular Biology, University of Ferrara, I 44121 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"722","DOI":"10.3324\/haematol.12427","article-title":"The Italian AICE-Genetics hemophilia A database: Results and correlation with clinical 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