{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,11,27]],"date-time":"2024-11-27T05:32:44Z","timestamp":1732685564978,"version":"3.28.2"},"reference-count":19,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T00:00:00Z","timestamp":1723593600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Cenerimod is a sphingosine\u20101\u2010phosphate receptor 1 modulator that reduces tissue availability of circulating lymphocytes. The compound is in Phase\u00a03 development for the treatment of systemic lupus erythematosus. Its pharmacokinetic properties are characterized by slow absorption and multiphasic elimination with a long terminal half\u2010life (t<jats:sub>\u00bd<\/jats:sub>), potentially caused by enterohepatic circulation (EHC). In this trial in healthy participants, oral cenerimod 0.5 and 4\u00a0mg once daily was administered for 50 days, followed by oral administration of activated charcoal (ie, 50 mg every 12 h for 11 days, starting 24 h after the last cenerimod dose), to investigate the potential EHC of cenerimod and assess whether elimination of cenerimod can be accelerated. The multiple\u2010dose pharmacokinetics, pharmacodynamics, safety, and tolerability of cenerimod were also evaluated. For both doses, peak plasma concentrations were reached 6 and 7\u00a0h after dosing. Cenerimod accumulated approximately eightfold and (near) steady\u2010state conditions were reached after 50 doses, resembling clinically meaningful exposure to cenerimod. The t<jats:sub>\u00bd<\/jats:sub> following 0.5 and 4 mg of cenerimod was 767\u00a0and 799 h (ie, 32 and 33 days) and 720 and 780\u00a0h (ie, 30 and 33 days) with or without administration of charcoal, respectively, indicating no statistically significant difference. Therefore, charcoal did not accelerate cenerimod elimination suggesting that there is no EHC of cenerimod. A reversible, dose\u2010dependent decrease in total lymphocyte count was observed. No safety concerns were identified; administration of charcoal was well tolerated.<\/jats:p>","DOI":"10.1002\/jcph.6106","type":"journal-article","created":{"date-parts":[[2024,8,14]],"date-time":"2024-08-14T15:53:40Z","timestamp":1723650820000},"page":"1566-1575","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multiple\u2010dose pharmacokinetics of cenerimod and the effect of charcoal on its elimination"],"prefix":"10.1002","volume":"64","author":[{"given":"Markus S.","family":"Mueller","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology Idorsia Pharmaceuticals Ltd  Allschwil Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre\u2010Eric","family":"Juif","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Idorsia Pharmaceuticals Ltd  Allschwil Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hakim","family":"Charfi","sequence":"additional","affiliation":[{"name":"Biotrial  Rennes France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jasper","family":"Dingemanse","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology Idorsia Pharmaceuticals Ltd  Allschwil Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,8,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20091343"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2016.1196188"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.370"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18122636"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1136\/lupus\u20102019\u2010000354"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrrheum.2016.186"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.3109\/03009742.2012.677857"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/Fs12016\u2010017\u20108640\u20105"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/art.11262"},{"key":"e_1_2_10_11_1","first-page":"903","article-title":"POS1147 Efficacy of cenerimod in patients with high IFN\u20101 gene expression signature and high anti\u2010DSDNA antibody levels: post\u2010hoc analysis from a phase 2 study","volume":"82","author":"Askanase A","year":"2023","journal-title":"Ann Rheum Dis"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1080\/00498254.2020.1736688"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12873"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.854"},{"key":"e_1_2_10_15_1","unstructured":"Carbomix\u00ae Summary of product characteristics: Carbomix\u00ae. 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