Clinical pharmacology, efficacy, and safety aspects of sphingosine-1-phosphate receptor modulators. (2nd August 2016)

• Record Type: Journal Article
• Authors: Juif, Pierre-Eric; Kraehenbuehl, Stephan; Dingemanse, Jasper
• Is Part Of: Expert opinion on drug metabolism and toxicology. Volume 12:Number 8(2016:Aug.)
• Page Start: 879
• Page End: 895
• Publication Date: 2016-08-02
• Subjects: Autoimmune diseases -- cardiodynamic effect -- fingolimod -- first dose -- lymphocytes -- ponesimod -- S1P1 receptor modulators; Drugs -- Toxicology -- Periodicals; Drugs -- Metabolism -- Periodicals; 615.7
• DOI: 10.1080/17425255.2016.1196188
• Languages: English
• ISSNs: 1742-5255

Abstract

ABSTRACT: Introduction : Sphingosine-1-phosphate (S1P) receptor modulators, of which one has received marketing approval and several others are in clinical development, display promising potential in the treatment of a spectrum of autoimmune diseases. Areas covered : Administration of S1P1 receptor modulators leads to functional receptor antagonism triggering sustained inhibition of the egress of lymphocytes from lymphoid organs. First-dose administration is associated with transient cardiovascular effects. We compiled and discussed available pharmacokinetic, pharmacodynamic, and safety data of selective and non-selective S1P receptor modulators that were investigated in recent years. Expert opinion : 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.