{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T17:03:55Z","timestamp":1781629435775,"version":"3.54.5"},"reference-count":26,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,6,5]],"date-time":"2018-06-05T00:00:00Z","timestamp":1528156800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100004330","name":"GlaxoSmithKline","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004330","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Pharm in Drug Dev"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>GSK2330672 is an inhibitor of the ileal bile acid transporter, designed to have minimal systemic exposure, and is under development as a potential therapeutic for pruritus associated with primary biliary cholangitis and other cholestatic liver diseases. A phase 1, double\u2010blind, placebo\u2010controlled, 4\u2010period crossover study was conducted to evaluate the safety, tolerability, and pharmacokinetic\/pharmacodynamic characteristics of GSK2330672 in healthy Japanese participants. Sixteen healthy male participants received single oral doses of GSK2330672 (10\u2010180 mg) or placebo in each period. No serious adverse events and no adverse events leading to study discontinuation or withdrawal were reported. Drug\u2010related adverse events reported included gastrointestinal symptoms (mostly diarrhea) and positive fecal occult blood tests, and were all mild and resolved without any interventions. GSK2330672 was undetectable in the majority of participants\u2019 plasma. Pharmacodynamic observations included a tendency for total serum bile acids to reduce and for serum 7\u03b1\u2010hydroxy\u20104\u2010cholesten\u20103\u2010one, a key intermediate of bile acid synthesis, to increase with increasing doses of GSK2330672. In the context of recently published indications of potential efficacy for cholestatic pruritus in non\u2010Japanese populations, these data support further evaluations of GSK2330672 in Japanese patients.<\/jats:p>","DOI":"10.1002\/cpdd.576","type":"journal-article","created":{"date-parts":[[2018,6,5]],"date-time":"2018-06-05T16:30:25Z","timestamp":1528216225000},"page":"70-77","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Evaluations Following Single Oral Doses of GSK2330672 in Healthy Japanese Volunteers"],"prefix":"10.1002","volume":"8","author":[{"given":"Hiroko","family":"Ino","sequence":"first","affiliation":[{"name":"GlaxoSmithKline Development &amp; Medical Affairs Division  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Endo","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Development &amp; Medical Affairs Division  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Wakamatsu","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Development &amp; Medical Affairs Division  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Ogura","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Development &amp; Medical Affairs Division  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yotaro","family":"Numachi","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Development &amp; Medical Affairs Division  Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stuart","family":"Kendrick","sequence":"additional","affiliation":[{"name":"GlaxoSmithKline Research &amp; Development  Stevenage UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,6,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2009.11.027"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-020712-164014"},{"key":"e_1_2_7_4_1","volume-title":"Principles and Practice of Hepatobiliary Diseases","author":"Dancygier H.","year":"2010"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2009.04.009"},{"key":"e_1_2_7_6_1","doi-asserted-by":"crossref","first-page":"351","DOI":"10.7861\/clinmedicine.15-4-351","article-title":"Drug treatment of pruritus in liver diseases","volume":"15","author":"Hegade VS","year":"2015","journal-title":"Clin Med"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1542-3565(03)00134-4"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/flgastro-2015-100618"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26365"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.12.005"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1509840"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/1756283X16630712"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R900012-JLR200"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M306370200"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.52.9.1239"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.52.9.1371"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/apt.13457"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27973"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.10.024"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/cld.613"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm400459m"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/dom.12656"},{"issue":"1","key":"e_1_2_7_23_1","first-page":"A305","article-title":"Single doses of an iBAT (SLC10A2) inhibitor suppress 24h serum bile acid concentrations and enhance bile acid synthesis","volume":"62","author":"Dobbins RL","year":"2013","journal-title":"Diabetes"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(17)30319-7"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.D200043-JLR200"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R900010-JLR200"},{"issue":"1","key":"e_1_2_7_27_1","first-page":"71","article-title":"Guidelines for the management of primary biliary cirrhosis (supported by the Ministry of Health, Labour and Welfare of Japan)","volume":"44","author":"The Intractable Hepatobiliary Disease Study Group","year":"2014","journal-title":"Hepatol Res"}],"container-title":["Clinical Pharmacology in Drug Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcpdd.576","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpdd.576","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T18:54:57Z","timestamp":1694285697000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/cpdd.576"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,6,5]]},"references-count":26,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2019,1]]}},"alternative-id":["10.1002\/cpdd.576"],"URL":"https:\/\/doi.org\/10.1002\/cpdd.576","archive":["Portico"],"relation":{},"ISSN":["2160-763X","2160-7648"],"issn-type":[{"value":"2160-763X","type":"print"},{"value":"2160-7648","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,6,5]]},"assertion":[{"value":"2017-10-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-06-05","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}