{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T10:16:29Z","timestamp":1792664189649,"version":"4.5.0"},"reference-count":23,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2011,7,19]],"date-time":"2011-07-19T00:00:00Z","timestamp":1311033600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Haemophilia"],"published-print":{"date-parts":[[2012,1]]},"abstract":"<jats:p><jats:bold>Summary.\u2002<\/jats:bold> N8 is a new recombinant factor VIII (rFVIII) compound produced and formulated without human\u2010 or animal\u2010derived protein. The aims of the present studies were to evaluate the pharmacokinetics and pharmacodynamics properties of N8 and to compare with a commercially available rFVIII product (Advate<jats:sup>\u00ae<\/jats:sup>) in haemophilia A mice. The pharmacokinetics were evaluated after single i.v. administration of 80, 120 and 280\u2003IU\u2003kg<jats:sup>\u22121<\/jats:sup> of N8 and Advate<jats:sup>\u00ae<\/jats:sup> and measurements of FVIII blood concentrations as a function of time. The efficacy and dose response curves of N8 and Advate<jats:sup>\u00ae<\/jats:sup> (1\u2013200\u2003IU\u2003kg<jats:sup>\u22121<\/jats:sup>) were evaluated in a tail bleeding model. Furthermore, the effects in a newly developed haemophilia knee joint haemarthrosis model were investigated. No significant differences were found in the pharmacokinetic parameters between N8 and Advate<jats:sup>\u00ae<\/jats:sup>. The clearances were 11\u2003\u00b1\u20031 vs. 10\u2003\u00b1\u20032\u2003mL\u2003h<jats:sup>\u22121<\/jats:sup>\u2003kg<jats:sup>\u22121<\/jats:sup> (<jats:italic>P<\/jats:italic>\u2003=\u20030.14) and the half\u2010lives 7.2\u2003\u00b1\u20030.9 vs. 7.7\u2003\u00b1\u20031.4\u2003h (<jats:italic>P<\/jats:italic>\u2003=\u20030.31) after administration of N8 and Advate<jats:sup>\u00ae<\/jats:sup> respectively. Dose\u2010independent pharmacokinetics was shown, and comparable efficacy and potency were shown between N8 and Advate<jats:sup>\u00ae<\/jats:sup> in the tail bleeding model. Both compounds normalized the bleeding at the dose of 200\u2003IU\u2003kg<jats:sup>\u22121<\/jats:sup>, and for blood loss ED<jats:sub>50<\/jats:sub> values of 27\u2003IU\u2003kg<jats:sup>\u22121<\/jats:sup> (N8) and 28\u2003IU\/kg (Advate<jats:sup>\u00ae<\/jats:sup>) were found (<jats:italic>P<\/jats:italic>\u2003=\u20030.97). In the haemarthrosis model, treatment with N8 and Advate<jats:sup>\u00ae<\/jats:sup> at 200\u2003IU\u2003kg<jats:sup>\u22121<\/jats:sup> reduced the mean increase in the joint diameter significantly from 1.23\u2003\u00b1\u20030.19 to 0.32\u2003\u00b1\u20030.08\u2003mm (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.01) and 0.25\u2003\u00b1 0.08\u2003mm (<jats:italic>P<\/jats:italic>\u2003&lt;\u20030.001) respectively. Pharmacokinetics and pharmacodynamics of N8 and Advate<jats:sup>\u00ae<\/jats:sup> were comparable after i.v. administration to haemophilia A mice.<\/jats:p>","DOI":"10.1111\/j.1365-2516.2011.02608.x","type":"journal-article","created":{"date-parts":[[2011,7,19]],"date-time":"2011-07-19T22:40:20Z","timestamp":1311115220000},"page":"139-145","source":"Crossref","is-referenced-by-count":33,"title":["Pharmacokinetics and pharmacodynamics of a new recombinant FVIII (N8) in haemophilia A mice"],"prefix":"10.1111","volume":"18","author":[{"given":"T.","family":"ELM","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D. M.","family":"KARPF","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.","family":"\u00d8VLISEN","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.","family":"PELZER","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"EZBAN","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"KJALKE","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"TRANHOLM","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,7,19]]},"reference":[{"key":"e_1_2_9_2_2","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1615621"},{"key":"e_1_2_9_3_2","volume-title":"Treatment of Hemophilia","author":"Kasper CK","year":"2008"},{"key":"e_1_2_9_4_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2516.2002.00615.x"},{"key":"e_1_2_9_5_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa067659"},{"key":"e_1_2_9_6_2","first-page":"1164","article-title":"Primary prophylaxis prevents the onset of arthropathy: longitudinal results of 603 boys with severe factor VIII deficiency analyzed through the Centers for Disease Control Universal Data Collection (CDC UDC) study","volume":"112","author":"Manco\u2010Johnson MJ","year":"2008","journal-title":"Blood"},{"key":"e_1_2_9_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2009.02135.x"},{"key":"e_1_2_9_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2010.02333.x"},{"key":"e_1_2_9_9_2","first-page":"06P46","article-title":"A multi\u2010centre, multi\u2010national, open\u2010label sequential trial comparing pharmacokinetics and safety of a new recombinant FVIII compound (N8) and advate in patients with haemophilia 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