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

Abstract

1. Cenerimod is a sphingosine-1-phosphate 1 receptor modulator under development for treatment of systemic lupus erythematosus.

2. 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 ¹⁴C-cenerimod.

3. 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.

4. 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.

Keywords:

• Cenerimod
• S1P1 receptor modulator
• ADME
• mass balance
• humans
• pharmacokinetics

Acknowledgments

The authors thank the study team at PRA Health Services (Groningen, The Netherlands) for the clinical conduct of this study, Radka Štěpánová (Aprova s.r.o., Brno, Czech Republic) for statistical analysis of clinical data, and Henk Poelman and his team (PRA Health Sciences – Early Development Services Bioanalytical Laboratory, Assen, The Netherlands) for the radioactivity quantification. The authors are also thankful to the Pharmaron team (Germantown, MD, USA) and the A&M team (Bergheim, Germany) for their work on metabolite profiling, quantification, and identification.

Disclosure statement

No potential conflict of interest was reported by the author(s).