Clinical pharmacology, efficacy, and safety aspects of sphingosine-1-phosphate receptor modulators

Abstract

The safety profile of S1P receptor modulators is considered better than other classes of immunomodulators and was further improved by the development of up-titration regimens to mitigate first-dose effects. S1P receptor modulators display similar pharmacodynamic effects but have very different pharmacokinetic profiles. Drugs with a rapid elimination are of interest in case of opportunistic infections or pregnancy, whereas the need of re-initiation of up-titration in case of treatment interruption can present a challenge.

Modelling pharmacokinetics and pharmacodynamics of the selective S1P1 receptor modulator cenerimod in healthy subjects and systemic lupus erythematosus patients

“…In Phase I studies, the number of subjects experiencing at least 1 adverse event was comparable following cenerimod and placebo treatment . A transient heart rate decrease following treatment initiation, as reported for most S1P receptor modulators, was observed.…”

Next generation of small molecules in inflammatory bowel disease

“…Although S1PR modulators appear to have a better safety profile than other classes of immunomodulators,85 some safety concerns persist. Fingolimod (Gylenia, Novartis) is a non-selective S1PR modulator (binding to S1P 1 , S1P 3 , S1P 4 and S1P 5 ) that has been approved by the FDA and the EMA for the treatment of relapsing-remitting multiple sclerosis 86.…”

Effects of High‐ and Low‐Fat Meals on the Pharmacokinetics of Ozanimod, a Novel Sphingosine‐1‐Phosphate Receptor Modulator

“…Sphingosine‐1‐phosphate (S1P) is an active phospholipid that binds to a family of 5 different G‐protein‐coupled receptor subtypes (S1P 1–5R ). S1P and its receptors regulate a variety of processes in the immune, cardiovascular, pulmonary, and nervous systems . S1P receptors are differentially expressed on a wide variety of cells.…”

“…S1P and its receptors regulate a variety of processes in the immune, cardiovascular, pulmonary, and nervous systems. 5,6 S1P receptors are differentially expressed on a wide variety of cells. S1P 1R , S1P 2R , and S1P 3R are ubiquitously present in the immune, cardiovascular, and central nervous systems.…”