Pharmacokinetics of S1P receptor modulators in the treatment of ulcerative colitis

Expert Opin Drug Metab Toxicol. 2024 Sep;20(9):881-892. doi: 10.1080/17425255.2024.2402931. Epub 2024 Sep 12.

Abstract

Introduction: Ulcerative colitis is a chronic inflammatory bowel disease, affecting the colorectal mucosae, with a relapsing-remitting course, characterized by the trafficking and gathering of lymphocytes in the inflammatory intestinal mucosa. Sphingosine-1-phosphate (S1P) receptor modulators preventing lymphocytes egress from lymphoid tissues to the active inflammation site is an alternative therapeutic option in this condition.

Area covered: We carried out a comprehensive review of the literature available on Medline, Scopus and Embase regarding the pharmacokinetics of S1P receptor modulators. For each compound, we reviewed the mechanism of action, pharmacokinetic data and efficacy and safety data from phase 3 studies and real-life studies when available.

Expert opinion: S1P receptor modulators, including ozanimod and etrasimod (both currently on the market) as well as VTX002 (under development), are a new class of drugs for the treatment of moderate to severe ulcerative colitis, inducing and maintaining the remission. Due to its pharmacokinetic features, this class of drugs has certain advantages such as an oral administration, a short half-life, a high volume of distribution, and no immunogenicity. On the other hand, there are risks of cardiological and ophthalmological side-effects, as well as drug-drug interactions risk, that require special attention from the healthcare providers.

Keywords: Ozanimod; VTX002; etrasimod; pharmacokinetics; sphingosine-1-phosphate receptor modulators; ulcerative colitis.

Publication types

  • Review

MeSH terms

  • Animals
  • Colitis, Ulcerative* / drug therapy
  • Drug Interactions
  • Half-Life
  • Humans
  • Indans
  • Intestinal Mucosa / metabolism
  • Lymphocytes / drug effects
  • Lymphocytes / metabolism
  • Oxadiazoles / administration & dosage
  • Oxadiazoles / adverse effects
  • Oxadiazoles / pharmacokinetics
  • Oxadiazoles / pharmacology
  • Severity of Illness Index
  • Sphingosine 1 Phosphate Receptor Modulators* / administration & dosage
  • Sphingosine 1 Phosphate Receptor Modulators* / adverse effects
  • Sphingosine 1 Phosphate Receptor Modulators* / pharmacokinetics
  • Sphingosine 1 Phosphate Receptor Modulators* / pharmacology
  • Sphingosine-1-Phosphate Receptors / metabolism

Substances

  • ozanimod
  • Sphingosine 1 Phosphate Receptor Modulators
  • Oxadiazoles
  • Sphingosine-1-Phosphate Receptors
  • Indans