{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T05:27:52Z","timestamp":1768454872472,"version":"3.49.0"},"reference-count":27,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2012,7,20]],"date-time":"2012-07-20T00:00:00Z","timestamp":1342742400000},"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":[[2012,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The objective of the present study was to evaluate the pharmacokinetic (<jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>) and pharmacodynamic (<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>) profiles of the new recombinant <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> compound turoctocog alfa and a Glyco\u2010PEGylated <jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> derivative thereof (<jats:styled-content style=\"fixed-case\">N8\u2010GP<\/jats:styled-content>) in Haemophilia A dogs. Six haemophilic dogs divided into two groups were included in the study. Each dog was administered a dose of 125\u00a0U\u00a0kg<jats:sup>\u22121<\/jats:sup>, blood samples were collected at predetermined time points for both pharmacokinetic (<jats:styled-content style=\"fixed-case\">FVIII<\/jats:styled-content> measured by one\u2010stage <jats:styled-content style=\"fixed-case\">aPTT<\/jats:styled-content> assay) and pharmacodynamic [whole blood clotting time (<jats:styled-content style=\"fixed-case\">WBCT<\/jats:styled-content>)] evaluations. After intravenous administration to haemophilic dogs, the plasma concentration at the first sampling point was comparable for turoctocog alfa and <jats:styled-content style=\"fixed-case\">N8\u2010GP<\/jats:styled-content>, and the clearance was estimated to be 6.5 and 3.9\u00a0mL\u00a0h<jats:sup>\u22121<\/jats:sup>kg<jats:sup>\u22121<\/jats:sup> for turoctocog alfa and <jats:styled-content style=\"fixed-case\">N8\u2010GP<\/jats:styled-content> respectively. Both turoctocog alfa and <jats:styled-content style=\"fixed-case\">N8\u2010GP<\/jats:styled-content> were able to reduce the <jats:styled-content style=\"fixed-case\">WBCT<\/jats:styled-content> time to normal levels (&lt;20\u00a0min), however, the reduced clearance was reflected in the <jats:styled-content style=\"fixed-case\">WBCT<\/jats:styled-content>, which returned to baseline at a later time point for <jats:styled-content style=\"fixed-case\">N8\u2010GP<\/jats:styled-content> as compared with dogs dosed with turoctocog alfa. The clearance was 40% reduced for <jats:styled-content style=\"fixed-case\">N8\u2010GP<\/jats:styled-content> as compared with turoctocog alfa. Simulations of a multiple dosing regimen in dogs, suggest that to maintain <jats:styled-content style=\"fixed-case\">WBCT<\/jats:styled-content> &lt;20\u00a0min <jats:styled-content style=\"fixed-case\">N8\u2010GP<\/jats:styled-content> can be dosed at reduced intervals, e.g. with 4\u00a0days between doses, whereas turoctocog alfa will have to be dosed with 2\u00bd day between doses. Data thereby supports <jats:styled-content style=\"fixed-case\">N8\u2010GP<\/jats:styled-content> as an alternative to standard <jats:styled-content style=\"fixed-case\">rFVIII<\/jats:styled-content> replacement therapy, with a more convenient dosing regimen.<\/jats:p>","DOI":"10.1111\/j.1365-2516.2012.02896.x","type":"journal-article","created":{"date-parts":[[2012,7,20]],"date-time":"2012-07-20T22:35:10Z","timestamp":1342823710000},"page":"941-947","source":"Crossref","is-referenced-by-count":35,"title":["Pharmacokinetics and pharmacodynamics of turoctocog alfa and <scp>N8<\/scp>\u2010<scp>GP<\/scp> in haemophilia <scp>A<\/scp> dogs"],"prefix":"10.1111","volume":"18","author":[{"given":"H.","family":"Agers\u00f8","sequence":"first","affiliation":[{"name":"Biopharm Research Unit Novo Nordisk A\/S Maaloev Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H. R.","family":"Stennicke","sequence":"additional","affiliation":[{"name":"Biopharm Research Unit Novo Nordisk A\/S Maaloev Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Pelzer","sequence":"additional","affiliation":[{"name":"Biopharm Research Unit Novo Nordisk A\/S Maaloev Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. N.","family":"Olsen","sequence":"additional","affiliation":[{"name":"Biopharm Research Unit Novo Nordisk A\/S Maaloev Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E. P.","family":"Merricks","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of North Carolina Chapel Hill NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N. A.","family":"deFriess","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of North Carolina Chapel Hill NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T. C.","family":"Nichols","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of North Carolina Chapel Hill NC USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Ezban","sequence":"additional","affiliation":[{"name":"Biopharm Research Unit Novo Nordisk A\/S Maaloev Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2012,7,20]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2010.02318.x"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa067659"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2006.01260.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2009.02135.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2010.02481.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2011.02608.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2011.02580.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2011.02495.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"crossref","unstructured":"StennickeHR KjalkeM KarpfDet\u00a0al.A Novel B\u2010Domain O\u2010glycoPEGylated FVIII (N8\u2010GP) Demonstrates Full Efficacy and Prolonged Effect in Hemophilic Mice Models Submitted 2012.","DOI":"10.1182\/blood-2012-01-407494"},{"issue":"4","key":"e_1_2_7_11_1","first-page":"40","volume":"16","author":"Stennicke R","year":"2010","journal-title":"Haemophilia"},{"issue":"2","key":"e_1_2_7_12_1","first-page":"116","volume":"9","author":"Elm T","year":"2011","journal-title":"J Thromb Haemost"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2011.02.013"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm9909645"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0037-1613091"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2011-02-336172"},{"issue":"2","key":"e_1_2_7_17_1","first-page":"28","article-title":"Preclinical studies of recombinant factor IX","volume":"35","author":"Schaub R","year":"1998","journal-title":"Semin Hematol"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2010.240"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard.2008.101659"},{"key":"e_1_2_7_20_1","unstructured":"R Development Core Team.R: A Language and Environment for Statistical Computing.R Foundation for Statistical Computing 2009. 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