{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T20:31:34Z","timestamp":1759177894384,"version":"3.41.2"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,9,14]],"date-time":"2017-09-14T00:00:00Z","timestamp":1505347200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cardiovascular Therapeutics"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>To characterize the single\u2010dose pharmacokinetics (<jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content>) and pharmacodynamics (<jats:styled-content style=\"fixed-case\">PD<\/jats:styled-content>) of bococizumab, a monoclonal antibody inhibiting proprotein convertase subtilisin\/kexin type 9 (<jats:styled-content style=\"fixed-case\">PCSK<\/jats:styled-content>9), administered subcutaneously (s.c.) to the abdomen, thigh, or upper arm (<jats:styled-content style=\"fixed-case\">NCT<\/jats:styled-content>02043301).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Seventy\u2010five adults with low\u2010density lipoprotein cholesterol (<jats:styled-content style=\"fixed-case\">LDL<\/jats:styled-content>\u2010C) \u2265130\u00a0mg\/<jats:styled-content style=\"fixed-case\">dL<\/jats:styled-content> and not on background lipid\u2010lowering therapy were randomized (1:1:1) to a single 150\u2010mg s.c. dose of bococizumab administered to the abdomen, thigh, or upper arm. Blood samples for bococizumab and lipids were collected for 12\u00a0weeks postdose.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Plasma bococizumab concentration\u2010time profiles and <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content> parameters were generally similar across injection sites. Mean maximum observed concentration (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>) ranged from 8.14 to 11.9\u00a0\u03bcg\/<jats:styled-content style=\"fixed-case\">mL<\/jats:styled-content>, and area under the concentration\u2010time curve (<jats:styled-content style=\"fixed-case\">AUC<\/jats:styled-content><jats:sub>inf<\/jats:sub>) ranged from 160.3 to 198.9\u00a0\u00b5g\u2219day\/mL. The median time to <jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub> (<jats:italic>T<\/jats:italic><jats:sub>max<\/jats:sub>) ranged from 4.25 to 6.93\u00a0days. Similar\u00a0<jats:styled-content style=\"fixed-case\">LDL<\/jats:styled-content>\u2010C concentration\u2010time profiles were observed across injection sites, with mean (% coefficient of variation) maximum reductions in <jats:styled-content style=\"fixed-case\">LDL<\/jats:styled-content>\u2010C of \u221257.5% (15.8), \u221257.0% (25.9), and \u221255.0% (24.1) for the abdomen, thigh, and upper arm, respectively. Adverse events (<jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>s) were mostly mild and generally similar across injection sites. Commonly reported <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content>s were upper respiratory tract infection (9.3%), headache (6.7%), and injection site reaction (6.7%). One serious <jats:styled-content style=\"fixed-case\">AE<\/jats:styled-content> was reported (ischemic colitis), which was not considered related to study drug.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Similar <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content> profiles and robust <jats:styled-content style=\"fixed-case\">LDL<\/jats:styled-content>\u2010C reductions were observed following a single 150\u2010mg s.c. injection of bococizumab administered to the abdomen, thigh, or upper arm in untreated subjects with <jats:styled-content style=\"fixed-case\">LDL<\/jats:styled-content>\u2010C \u2265130\u00a0mg\/<jats:styled-content style=\"fixed-case\">dL<\/jats:styled-content>. Bococizumab was generally well tolerated following a single 150\u2010mg s.c. administration in this subject population.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1755-5922.12278","type":"journal-article","created":{"date-parts":[[2017,6,21]],"date-time":"2017-06-21T09:12:43Z","timestamp":1498036363000},"source":"Crossref","is-referenced-by-count":11,"title":["Pharmacokinetics and pharmacodynamics of bococizumab, a monoclonal antibody to <scp>PCSK<\/scp>9, after single subcutaneous injection at three sites [<scp>NCT<\/scp> 02043301]"],"prefix":"10.1111","volume":"35","author":[{"given":"Ellen Q.","family":"Wang","sequence":"first","affiliation":[{"name":"Clinical Pharmacology Global Product Development Pfizer Inc  New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Plotka","sequence":"additional","affiliation":[{"name":"Global Biometrics and Data Management Global Product Development  Pfizer Inc, Collegeville PA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joanne","family":"Salageanu","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology Global Product Development Pfizer Inc  Groton CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Catherine","family":"Sattler","sequence":"additional","affiliation":[{"name":"Clinical Sciences and Operations Global Product Development Pfizer Inc  Groton CT USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carla","family":"Yunis","sequence":"additional","affiliation":[{"name":"Global Product Development CVMET Therapeutics Pfizer Inc  New York NY USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,9,14]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0000000000000137"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.03.099"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.114.301621"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrcardio.2014.84"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1500858"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1501031"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2015.02.006"},{"key":"e_1_2_9_9_1","article-title":"Statins for the primary prevention of cardiovascular disease","author":"Taylor F","year":"2011","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11883-014-0414-4"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOL.0000000000000021"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1097\/MED.0000000000000242"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.111.187419"},{"key":"e_1_2_9_14_1","unstructured":"Pfizer Inc.Pfizer discontinues global development of bococizumab its investigational PCSK9 inhibitor.2016.www.pfizer.com\/news\/press-release\/press-release-detail\/pfizer_discontinues_global_development_of_bococizumab_its_investigational_pcsk9_inhibitor. 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