{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T11:15:17Z","timestamp":1791544517211,"version":"4.3.4"},"reference-count":25,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2015,2,2]],"date-time":"2015-02-02T00:00:00Z","timestamp":1422835200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Shire, Eysins, Switzerland"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Purpose<\/jats:title><jats:p>Icatibant is a bradykinin\u20102 receptor antagonist approved to treat acute hereditary angioedema attacks in adults. To\u2010date, no thorough investigation of the clinical pharmacokinetic (PK) parameters of icatibant and its primary metabolites has been reported. Here we present the PK results of two phase I clinical studies of icatibant in healthy human volunteers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Single\u2010 and multiple\u2010dose plasma pharmacokinetics of icatibant were characterized in healthy volunteers. Icatibant concentration\u2010time profiles and PK parameters were derived after a single 30\u2010 or 90\u2010mg dose or three 30\u2010mg doses given at 6\u2010hour intervals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Maximal plasma concentrations for the 30\u2010mg (979\u2009\u00b1\u2009262\u2009ng\/mL) and 90\u2010mg doses (2,719\u2009\u00b1\u2009666\u2009ng\/mL) were achieved at &lt;1\u2009hour postdose. The total plasma icatibant exposure for the 30\u2010 and 90\u2010mg doses was 2,191\u2009\u00b1\u2009565 and 6,736\u2009\u00b1\u20091,230\u2009h\u2009\u00b7\u2009ng\/mL, respectively, with elimination half\u2010life values of 1.48\u2009\u00b1\u20090.35 and 2.00\u2009\u00b1\u20090.57\u2009hours, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Single 30\u2010 and 90\u2010mg subcutaneous administration of icatibant exhibited dose\u2010proportional PK with no appreciable accumulation upon repeated 30\u2010mg doses administered at 6\u2010hour intervals.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cpdd.138","type":"journal-article","created":{"date-parts":[[2014,6,24]],"date-time":"2014-06-24T05:48:56Z","timestamp":1403588936000},"page":"105-111","source":"Crossref","is-referenced-by-count":25,"title":["Pharmacokinetics of single and repeat doses of icatibant"],"prefix":"10.1002","volume":"4","author":[{"given":"J. Kevin","family":"Leach","sequence":"first","affiliation":[{"name":"Shire Lexington MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Spencer","sequence":"additional","affiliation":[{"name":"Shire Lexington MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryann","family":"Mascelli","sequence":"additional","affiliation":[{"name":"Shire Lexington MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas G.","family":"McCauley","sequence":"additional","affiliation":[{"name":"Shire Lexington MA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,2,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(11)60935-5"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaci.2012.05.055"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.2147\/TCRM.S3172"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2010.05.010"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V68.2.455.455"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1081-1206(10)60493-0"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0065-2776(04)86005-X"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1081-1206(10)60580-7"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-6749(83)90052-0"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200214211"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0196-9781(85)90033-6"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.17.1.107"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.1991.tb12248.x"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2012.723692"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.anai.2011.08.015"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.2165\/11204500-000000000-00000"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1081-1206(10)60584-4"},{"key":"e_1_2_9_19_1","first-page":"333","article-title":"Consensus statement on the diagnosis, management, and treatment of angioedema mediated by bradykinin. Part I. Classification, epidemiology, pathophysiology, genetics, clinical symptoms, and diagnosis","volume":"21","author":"Caballero T","year":"2011","journal-title":"J Investig Allergol Clin Immunol."},{"key":"e_1_2_9_20_1","unstructured":"EMEA. Firazyr (icatibant) EPAR summary for the public. 2012; EMEA\/H\/C\/00899. London UK updated November 29 2012."},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0906393"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(97)09137-X"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200208223470820"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920009789895499"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005344-199200209-00003"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0625.2011.01410.x"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcpdd.138","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcpdd.138","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.138","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T18:17:03Z","timestamp":1696616223000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.138"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,2,2]]},"references-count":25,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2015,3]]}},"alternative-id":["10.1002\/cpdd.138"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.138","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,2,2]]}}}