{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,2]],"date-time":"2026-03-02T16:16:47Z","timestamp":1772468207269,"version":"3.50.1"},"reference-count":22,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,3,14]],"date-time":"2016-03-14T00:00:00Z","timestamp":1457913600000},"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":[[2016,7]]},"abstract":"Introduction<\/jats:title>Pharmacokinetic (PK<\/jats:styled-content>) studies on recombinant FIX<\/jats:styled-content> concentrate, Nonacog alpha, were conducted with different sampling time designs which gave rise to not complete and homogenous outcomes. In addition, patient's FIX<\/jats:styled-content> genotype\/PK<\/jats:styled-content> relationship has never been investigated.<\/jats:p><\/jats:sec>Aim<\/jats:title>Investigate how different sampling times may affect PK<\/jats:styled-content> parameters and try to find a FIX<\/jats:styled-content> genotype\/PK<\/jats:styled-content> relationship.<\/jats:p><\/jats:sec>Patients and Methods<\/jats:title>A cohort pharmacokinetic, Nonacog Alpha single\u2010dose, open\u2010label, non\u2010comparative study was conducted in eight Comprehensive Care Haemophilia Centres in Italy. Seventeen previously treated moderate or severe haemophilia B patients were enrolled. Factors IX<\/jats:styled-content>:C one\u2010stage clotting assay, FIX<\/jats:styled-content> genotype and PK<\/jats:styled-content> analysis were centralized.<\/jats:p><\/jats:sec>Results<\/jats:title>The evaluation of PK<\/jats:styled-content> outcomes showed a quite long half\u2010life, smaller clearance and volume of distribution of Nonacog Alpha in comparison with the results from previously reported studies, where blood sampling was stopped too early. The relationship between PK<\/jats:styled-content> outcomes and FIX<\/jats:styled-content> genotype showed that small deletions displayed the higher clearance and shorter half\u2010life, the nonsense mutations (the lower and the longer respectively), and missense mutations were in between.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>It is evident that area under the curve (AUC<\/jats:styled-content>) and other PK<\/jats:styled-content> parameters depend from the sampling time design. In order to have a complete evaluation of clotting factors in vivo<\/jats:italic> decay, blood samples must be collected until the baseline factor concentration has been achieved again. Due to the relationship between FIX<\/jats:styled-content> genotype and clearance, tailored prophylaxis of HB<\/jats:styled-content> patients could be partially predicted by genotyping.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hae.12916","type":"journal-article","created":{"date-parts":[[2016,3,18]],"date-time":"2016-03-18T12:14:46Z","timestamp":1458303286000},"page":"537-542","source":"Crossref","is-referenced-by-count":18,"title":["Correlation between FIX<\/scp> genotype and pharmacokinetics of Nonacog alpha according to a multicentre Italian study"],"prefix":"10.1111","volume":"22","author":[{"given":"M.","family":"Morfini","sequence":"first","affiliation":[{"name":"Past President of Italian Association of Haemophilia Centres (AICE) Firenze Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Dragani","sequence":"additional","affiliation":[{"name":"Haemophilia & Thrombosis Centre Haematology Department Regional Hospital Pescara Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Paladino","sequence":"additional","affiliation":[{"name":"Atherothrombotic Diseases Cardio\u2010Vascular Department University Hospital of Florence Florence Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Radossi","sequence":"additional","affiliation":[{"name":"Haematology and Haemophilia Centre Regional Hospital Castelfranco Veneto Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Di Minno","sequence":"additional","affiliation":[{"name":"Reference Centre for Haemophilia and Thrombosis Department of Clinical and Experimental Medicine Federico II University Naples Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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Maria della Misericordia Hospital Udine Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Napolitano","sequence":"additional","affiliation":[{"name":"Haemophilia & Thrombosis Centre Haematology Department University of Palermo Palermo Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Tagariello","sequence":"additional","affiliation":[{"name":"Haematology and Haemophilia Centre Regional Hospital Castelfranco Veneto Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,3,14]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1657536"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1537-2995.2002.00039.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V98.13.3600"},{"issue":"2","key":"e_1_2_8_5_1","first-page":"33","article-title":"Clinical evaluation of recombinant factor IX","volume":"35","author":"White GC","year":"1998","journal-title":"Semin Hematol"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2516.2001.00465.x"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2516.2007.01458.x"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0038-1646423"},{"key":"e_1_2_8_9_1","unstructured":"LeeM MorfiniM SchulmanS IngerslevJandthe Factor VIII\/Factor IX Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. 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