Absorption, distribution, metabolism, and excretion of cenerimod, a selective S1P1 receptor modulator in healthy subjects

• Published in: Xenobiotica Vol. 50; no. 8; pp. 947 - 956
• Main Authors: Boof, Marie-Laure, van Lier, Jan Jaap, English, Stephen, Fischer, Hartmut, Ufer, Mike, Dingemanse, Jasper
• Format: Journal Article
• Language: English
• Published: Taylor & Francis 02.08.2020
• Subjects: ADME; Cenerimod; humans; mass balance; pharmacokinetics; S1P1 receptor modulator
• ISSN: 0049-8254; 1366-5928; 1366-5928
• DOI: 10.1080/00498254.2020.1736688

Cenerimod is a sphingosine-1-phosphate 1 receptor modulator under development for treatment of systemic lupus erythematosus. This single-centre, open-label, single-dose study investigated the mass balance and excretion routes and aimed at identifying and quantifying cenerimod metabolites in plasma, urine, and faeces after oral administration of 2 mg/100 μCi (3.7 MBq) of 14 C-cenerimod. Total mean cumulative recovery was 84% of the administered dose (58-100% in faeces and 4.6-12% in urine). In a 0-504 h cross-subject area under the curve plasma pool, cenerimod and two metabolites were detected accounting for 78, 6.0, and 4.9% of total radioactivity, respectively, i.e. no major metabolite was identified in plasma. Cenerimod was only detected in faeces and accounted for 17% of the radioactivity excreted in this matrix. The metabolite M32 was detected in both urine and faeces and represented 23% and 66% of radioactivity excreted in these matrices, respectively. Other metabolites of unknown structure were detected in small amounts. Overall, M32 and cenerimod accounted for 52% and 13%, respectively, of the total radioactivity recovered. Among the excreted metabolites, only the non-enzymatically formed M32 represented more than 25% of total drug-related material. Therefore, no pharmacokinetic drug-drug interaction studies are foreseen.