Clinical pharmacology, efficacy, and safety aspects of sphingosine-1-phosphate receptor modulators
- 13 June 2016
- journal article
- review article
- Published by Taylor & Francis Ltd in Expert Opinion on Drug Metabolism & Toxicology
- Vol. 12 (8), 879-895
- https://doi.org/10.1080/17425255.2016.1196188
Abstract
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. 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. 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.Keywords
This publication has 88 references indexed in Scilit:
- Safety and efficacy of fingolimod in patients with relapsing-remitting multiple sclerosis (FREEDOMS II): a double-blind, randomised, placebo-controlled, phase 3 trialThe Lancet Neurology, 2014
- The outs and the ins of sphingosine-1-phosphate in immunityNature Reviews Immunology, 2011
- International Union of Basic and Clinical Pharmacology. LXXVIII. Lysophospholipid Receptor Nomenclature: TABLE 1Pharmacological Reviews, 2010
- Fingolimod (FTY720): discovery and development of an oral drug to treat multiple sclerosisNature Reviews Drug Discovery, 2010
- HDL and its sphingosine-1-phosphate content in cardioprotectionHeart Failure Reviews, 2007
- Sphingosine 1-phosphate and its receptors: an autocrine and paracrine networkNature Reviews Immunology, 2005
- Sphingosine-1-phosphate: an enigmatic signalling lipidNature Reviews Molecular Cell Biology, 2003
- The Immune Modulator FTY720 Targets Sphingosine 1-Phosphate ReceptorsJournal of Biological Chemistry, 2002
- Characterization of a Novel Sphingosine 1-Phosphate Receptor, Edg-8Online Journal of Public Health Informatics, 2000
- EDG6, a Novel G-Protein-Coupled Receptor Related to Receptors for Bioactive Lysophospholipids, Is Specifically Expressed in Lymphoid TissueGenomics, 1998