{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:10:18Z","timestamp":1790662218100,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,8,28]],"date-time":"2017-08-28T00:00:00Z","timestamp":1503878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100005646","name":"Actelion Pharmaceuticals","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005646","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clin Pharma and Therapeutics"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:p>Lucerastat is a glucosylceramide synthase inhibitor aimed at reducing production of glycosphingolipids (GSLs), including those accumulating in Fabry disease. The safety, tolerability, pharmacodynamics, and pharmacokinetics of oral lucerastat were evaluated in an exploratory study in patients with Fabry disease. In this single\u2010center, open\u2010label, randomized study, 10 patients received lucerastat 1,000 mg b.i.d. for 12 weeks in addition to enzyme replacement therapy (ERT; the lucerastat group). Four patients with Fabry disease received ERT only. Eight patients reported 17 adverse events (AEs) in the lucerastat group. No clinically relevant safety abnormalities were observed. The mean (SD) levels of the plasma GSLs, glucosylceramide, lactosylceramide, and globotriaosylceramide, were significantly decreased from baseline in the lucerastat group (\u201049.0% (16.5%), \u201032.7% (13.0%), and \u201055.0% (10.4%), respectively). Lucerastat 1,000 mg b.i.d. was well tolerated in patients with Fabry disease over 12 weeks. A marked decrease in plasma GSLs was observed, suggesting clinical potential for lucerastat in patients with Fabry disease.<\/jats:p>","DOI":"10.1002\/cpt.790","type":"journal-article","created":{"date-parts":[[2017,7,12]],"date-time":"2017-07-12T08:56:51Z","timestamp":1499849811000},"page":"703-711","source":"Crossref","is-referenced-by-count":103,"title":["Lucerastat, an Iminosugar for Substrate Reduction Therapy: Tolerability, Pharmacodynamics, and Pharmacokinetics in Patients With Fabry Disease on Enzyme Replacement"],"prefix":"10.1111","volume":"103","author":[{"given":"Nicolas","family":"Gu\u00e9rard","sequence":"first","affiliation":[{"name":"Department of Global Clinical Pharmacology Idorsia Pharmaceuticals Ltd Allschwil Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Oder","sequence":"additional","affiliation":[{"name":"Fabry Center for Interdisciplinary Therapy (FAZiT), Comprehensive Heart Failure Center (CHFC), and Department of Internal Medicine I, Divisions of Cardiology and Nephrology, University Hospital W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Nordbeck","sequence":"additional","affiliation":[{"name":"Fabry Center for Interdisciplinary Therapy (FAZiT), Comprehensive Heart Failure Center (CHFC), and Department of Internal Medicine I, Divisions of Cardiology and Nephrology, University Hospital W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Zwingelstein","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Actelion Pharmaceuticals Ltd Allschwil Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Morand","sequence":"additional","affiliation":[{"name":"Department of Global Clinical Science Idorsia Pharmaceuticals Ltd Allschwil Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard W.D.","family":"Welford","sequence":"additional","affiliation":[{"name":"DD Biology, Translational Science, Idorsia Pharmaceuticals Ltd Allschwil Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jasper","family":"Dingemanse","sequence":"additional","affiliation":[{"name":"Department of Global Clinical Pharmacology Idorsia Pharmaceuticals Ltd Allschwil Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Wanner","sequence":"additional","affiliation":[{"name":"Fabry Center for Interdisciplinary Therapy (FAZiT), Comprehensive Heart Failure Center (CHFC), and Department of Internal Medicine I, Divisions of Cardiology and Nephrology, University Hospital W\u00fcrzburg W\u00fcrzburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,8,28]]},"reference":[{"key":"e_1_2_12_1_1","doi-asserted-by":"publisher","DOI":"10.1186\/1750-1172-5-30"},{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2013.163"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978-0-444-62702-5.00017-2"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2007.055210"},{"issue":"1","key":"e_1_2_12_5_1","first-page":"88","article-title":"Fabry disease","volume":"12","author":"Thomas A.S.","year":"2014","journal-title":"Pediatr. Endocrinol. Rev."},{"key":"e_1_2_12_6_1","volume-title":"Fabry Disease: Perspectives From 5 Years of FOS","author":"Ries M.","year":"2006"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2003.tb00222.x"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.38.11.769"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.38.11.750"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2009.01.003"},{"key":"e_1_2_12_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2016.07.001"},{"key":"e_1_2_12_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2012.08.003"},{"key":"e_1_2_12_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.285.21.2743"},{"key":"e_1_2_12_14_1","doi-asserted-by":"publisher","DOI":"10.1086\/318809"},{"key":"e_1_2_12_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0152812"},{"key":"e_1_2_12_16_1","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-146-2-200701160-00148"},{"key":"e_1_2_12_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgmr.2015.02.002"},{"key":"e_1_2_12_18_1","doi-asserted-by":"publisher","DOI":"10.1111\/joim.12077"},{"key":"e_1_2_12_19_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2006080816"},{"key":"e_1_2_12_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.0022-202X.2004.22425.x"},{"key":"e_1_2_12_21_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2002.00675.x"},{"key":"e_1_2_12_22_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200107053450102"},{"key":"e_1_2_12_23_1","doi-asserted-by":"publisher","DOI":"10.2119\/molmed.2015.00088"},{"key":"e_1_2_12_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10038-006-0369-6"},{"key":"e_1_2_12_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1523-1755.2004.00924.x"},{"key":"e_1_2_12_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-011-9400-y"},{"key":"e_1_2_12_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2008.10.013"},{"key":"e_1_2_12_28_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0047805"},{"key":"e_1_2_12_29_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2014121226"},{"key":"e_1_2_12_30_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1510198"},{"key":"e_1_2_12_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-016-0607-y"},{"issue":"1","key":"e_1_2_12_32_1","first-page":"S111","article-title":"Pharmacological chaperone therapy by active\u2010site\u2010specific chaperones in Fabry disease: in vitro and preclinical studies","volume":"47","author":"Germain D.P.","year":"2009","journal-title":"Int. J. Clin. Pharmacol. Ther."},{"key":"e_1_2_12_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.122"},{"key":"e_1_2_12_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2008.00656.x"},{"key":"e_1_2_12_35_1","doi-asserted-by":"publisher","DOI":"10.1358\/dot.2006.42.1.937457"},{"key":"e_1_2_12_36_1","doi-asserted-by":"publisher","DOI":"10.2147\/TCRM.S73226"},{"key":"e_1_2_12_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0015033"},{"key":"e_1_2_12_38_1","unstructured":"Welford R.W.D.et al.Lucerastat an iminosugar substrate reduction therapy for Fabry disease: preclinical evidence. 13th Annual WORLD Symposium San Diego CA 13\u201317 February2017. Abstract 360."},{"key":"e_1_2_12_39_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-017-0565-9"},{"key":"e_1_2_12_40_1","unstructured":"Guerard N. Zwingelstein C. Dingemanse J.Lucerastat an iminosugar for substrate reduction therapy: pharmacokinetics tolerability and safety in subjects with mild moderate and severe renal function impairment. 13th Annual WORLD Symposium San Diego CA 13\u201317 February2017. Abstract 122."},{"key":"e_1_2_12_41_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2015-103471"},{"key":"e_1_2_12_42_1","first-page":"79","article-title":"Recommendations for chamber quantification","volume":"7","author":"Lang R.M.","year":"2006","journal-title":"Eur. Heart J. Cardiovasc. Imaging"},{"key":"e_1_2_12_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0957-4166(99)00468-1"},{"key":"e_1_2_12_44_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-015-0297-7"},{"key":"e_1_2_12_45_1","doi-asserted-by":"publisher","DOI":"10.1007\/8904_2015_483"},{"key":"e_1_2_12_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2010.09.007"},{"key":"e_1_2_12_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/1873-3468.12104"},{"key":"e_1_2_12_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-016-0413-3"},{"key":"e_1_2_12_49_1","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2013060585"},{"key":"e_1_2_12_50_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986712800784739"}],"container-title":["Clinical Pharmacology &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcpt.790","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.790","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cpt.790","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cpt.790","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,7]],"date-time":"2023-11-07T13:32:43Z","timestamp":1699363963000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1002\/cpt.790"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,8,28]]},"references-count":50,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2018,4]]}},"alternative-id":["10.1002\/cpt.790"],"URL":"https:\/\/doi.org\/10.1002\/cpt.790","archive":["Portico"],"relation":{},"ISSN":["0009-9236","1532-6535"],"issn-type":[{"value":"0009-9236","type":"print"},{"value":"1532-6535","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,8,28]]}}}