Absorption, distribution, metabolism, and excretion of cenerimod, a selective S1P1 receptor modulator in healthy subjects. (2nd August 2020)

• Record Type: Journal Article
• Authors: Boof, Marie-Laure; van Lier, Jan Jaap; English, Stephen; Fischer, Hartmut; Ufer, Mike; Dingemanse, Jasper
• Is Part Of: Xenobiotica. Volume 50:Number 8(2020:Aug.)
• Page Start: 947
• Page End: 956
• Publication Date: 2020-08-02
• Subjects: Cenerimod -- S1P1 receptor modulator -- ADME -- mass balance -- humans -- pharmacokinetics; Metabolism -- Periodicals; Drugs -- Physiological effect -- Periodicals; Food additives -- Periodicals; Chemicals -- Physiological effect -- Periodicals; Biochemistry -- Periodicals; Pharmaceutical Preparations -- metabolism -- Periodicals; Metabolism -- Periodicals; 574.133
• DOI: 10.1080/00498254.2020.1736688
• Languages: English
• ISSNs: 0049-8254

Abstract

Abstract: 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.