{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T23:30:23Z","timestamp":1789947023710,"version":"4.0.1"},"reference-count":17,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,4,5]],"date-time":"2012-04-05T00:00:00Z","timestamp":1333584000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:sec>\n                    <jats:label\/>\n                    <jats:p>\n                      <jats:bold>WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT<\/jats:bold>\n                    <\/jats:p>\n                    <jats:p>\u2022\u2003Flupirtine has been on the market for about 30 years in several European countries as an analgesic. This use has not resulted in regulatory action concerning hepatotoxicity.<\/jats:p>\n                    <jats:p>\n                      <jats:bold>WHAT THIS STUDY ADDS<\/jats:bold>\n                    <\/jats:p>\n                    <jats:p>\u2022\u2003When used in a novel indication, hepatotoxicity was frequent with flupirtine, questioning the general assumption that the safety profile in one indication can be extrapolated to other indications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>AIMS<\/jats:title>\n                    <jats:p>To determine efficacy of the analgesic flupirtine in the treatment of overactive bladder syndrome in a proof\u2010of\u2010concept study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Double\u2010blind, double\u2010dummy, three\u2010armed comparison of flupirtine extended release (400\u2003mg\/day, titrated to 600\u2003mg\/day), tolterodine extended release (4\u2003mg\/day) and placebo for 12 weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>When major elevations of liver enzymes (more than three times the upper normal limit) were detected in several flupirtine\u2010exposed patients, the study was prematurely discontinued. Based on study\u2010end data, hepatotoxicity was detected in 31% of patients receiving flupirtine for \u22656 weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>Unexpected frequent and relevant toxicity can occur when testing an established drug for a new indication.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/j.1365-2125.2011.04138.x","type":"journal-article","created":{"date-parts":[[2011,11,2]],"date-time":"2011-11-02T05:03:28Z","timestamp":1320210208000},"page":"821-825","source":"Crossref","is-referenced-by-count":59,"title":["Unexpected frequent hepatotoxicity of a prescription drug, flupirtine, marketed for about 30 years"],"prefix":"10.1111","volume":"73","author":[{"given":"Martin C.","family":"Michel","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piotr","family":"Radziszewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Falconer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Marschall\u2010Kehrel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koenraad","family":"Blot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,4,5]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1124\/mol.108.049825"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2009.00111.x"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.2165\/11536230-000000000-00000"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1080\/03655230600895242"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.2010.514903"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-011-1022-7"},{"key":"e_1_2_6_8_2","first-page":"266","article-title":"Die Langzeitvertr\u00e4glichkeit von Flupirtin. Offene multizentrische Studie \u00fcber ein Jahr","volume":"111","author":"Herrmann WM","year":"1993","journal-title":"Fortschr Med"},{"key":"e_1_2_6_9_2","unstructured":"German Prescribing Information.Katadolon S long.2011. Available athttp:\/\/www.fachinfo.de(last accesssed 23 November 2011)."},{"key":"e_1_2_6_10_2","unstructured":"MichelMC RadziszeswskiP FalconerC Marschall\u2010KehrelD RundfeldtC VanhoutteF.The centrally acting ion channel modulator flupirtine improves bladder function in animal models and patients with overactive bladder syndrome.2008. Available athttp:\/\/www.icsoffice.org\/Abstracts\/Publish\/46\/000406pdf(last accesssed 13 May 2011)."},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.WNL.0000113764.35026.EF"},{"key":"e_1_2_6_12_2","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1111\/j.1742-1241.1985.tb07777.x","article-title":"Use of flupirtine maleate as an analgesic in patients with liver disease","volume":"39","author":"Powell\u2010Jackson P","year":"1985","journal-title":"Br J Clin Pract"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-011-1087-9"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra052270"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1185\/03007990802579769"},{"key":"e_1_2_6_16_2","first-page":"A3200","article-title":"Lebersch\u00e4den unter Flupirtin","volume":"104","author":"Arzneimittelkommission der deutschen \u00c4rzteschaft","year":"2007","journal-title":"Dtsch Arztebl"},{"key":"e_1_2_6_17_2","unstructured":"U.S.Department of Health and Human Services.Guidance for industry. Drug\u2010induced liver injury: premarketing clinical evaluation.2009. Available athttp:\/\/www.fda.gov\/downloads\/Drugs\/GuidanceComplianceRegulatoryInformation\/Guidances\/UCM174090pdf(last accesssed 3 October 2011)."},{"key":"e_1_2_6_18_2","unstructured":"European Commission.The rules governing medicinal products in the European Union Volume 9A.2008. Available athttp:\/\/ec.europa.eu\/health\/files\/eudralex\/vol\u20109\/pdf\/vol9a_09\u20102008_enpdf(last accesssed 3 October 2011)."}],"container-title":["British Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fj.1365-2125.2011.04138.x","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/j.1365-2125.2011.04138.x","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,15]],"date-time":"2023-10-15T19:23:53Z","timestamp":1697397833000},"score":1,"resource":{"primary":{"URL":"https:\/\/bpspubs.onlinelibrary.wiley.com\/doi\/10.1111\/j.1365-2125.2011.04138.x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,4,5]]},"references-count":17,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2012,5]]}},"alternative-id":["10.1111\/j.1365-2125.2011.04138.x"],"URL":"https:\/\/doi.org\/10.1111\/j.1365-2125.2011.04138.x","archive":["Portico"],"relation":{},"ISSN":["0306-5251","1365-2125"],"issn-type":[{"value":"0306-5251","type":"print"},{"value":"1365-2125","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,4,5]]}}}