{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T02:17:47Z","timestamp":1789438667384,"version":"build-2803163510"},"reference-count":14,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2015,5,22]],"date-time":"2015-05-22T00:00:00Z","timestamp":1432252800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004336","name":"Novartis","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004336","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2015,6]]},"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Serelaxin is a recombinant form of human relaxin\u20102 in development for treatment of acute heart failure. This study aimed to evaluate the pharmacokinetics (<jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>) of serelaxin in patients with hepatic impairment. Secondary objectives included evaluation of immunogenicity, safety and tolerability of serelaxin.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was an open\u2010label, parallel group study (<jats:styled-content style=\"fixed-case\">NCT01433458<\/jats:styled-content>) comparing the <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content> of serelaxin following a single 24\u2009h intravenous (i.v.) infusion (30\u2009\u03bcg\u2009kg<jats:sup>\u22121<\/jats:sup>\u2009day<jats:sup>\u22121<\/jats:sup>) between patients with mild, moderate or severe hepatic impairment (<jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>hild\u2013<jats:styled-content style=\"fixed-case\">P<\/jats:styled-content>ugh class <jats:styled-content style=\"fixed-case\">A<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">B<\/jats:styled-content>, <jats:styled-content style=\"fixed-case\">C<\/jats:styled-content>) and healthy matched controls. Blood sampling and standard safety assessments were conducted. Primary non\u2010compartmental <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content> parameters [including area under the serum concentration\u2013time curve AUC(0\u201348\u2009h) and AUC(0\u2013\u221e) and serum concentration at 24\u2009h post\u2010dose (<jats:styled-content style=\"fixed-case\"><jats:italic>C<\/jats:italic><jats:sub>24h<\/jats:sub><\/jats:styled-content>)] were compared between each hepatic impairment group and healthy controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 49 subjects (including 25 patients with hepatic impairment) were enrolled, of which 48 subjects completed the study. In all groups, the serum concentration of serelaxin increased over the first few hours of infusion, reached steady\u2010state at 12\u201324\u2009h and then declined following completion of infusion, with a mean terminal half\u2010life of 7\u20138\u2009h. All <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content> parameter estimates were comparable between each group of patients with hepatic impairment and healthy controls. No serious adverse events, discontinuations due to adverse events or deaths were reported. No serelaxin treatment\u2010related antibodies developed during this study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content> and safety profile of serelaxin were not affected by hepatic impairment. No dose adjustment is needed for serelaxin treatment of 48\u2009h i.v. infusion in patients with hepatic impairment.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.12572","type":"journal-article","created":{"date-parts":[[2014,12,16]],"date-time":"2014-12-16T06:09:31Z","timestamp":1418710171000},"page":"937-945","source":"Crossref","is-referenced-by-count":28,"title":["Pharmacokinetics of serelaxin in patients with hepatic impairment: a single\u2010dose, open\u2010label, parallel group study"],"prefix":"10.1111","volume":"79","author":[{"given":"Zhanna","family":"Kobalava","sequence":"first","affiliation":[{"name":"Peoples Friendship University of Russia  Moscow Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Villevalde","sequence":"additional","affiliation":[{"name":"Peoples Friendship University of Russia  Moscow 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