A novel CRTH2 antagonist: Single‐ and multiple‐dose tolerability, pharmacokinetics, and pharmacodynamics of ACT‐453859 in healthy subjects

@article{Ghin2015ANC,
  title={A novel CRTH2 antagonist: Single‐ and multiple‐dose tolerability, pharmacokinetics, and pharmacodynamics of ACT‐453859 in healthy subjects},
  author={M. G{\'e}hin and D. Strasser and J. Zisowsky and H. Farine and P. Groenen and J. Dingemanse and P. Sidharta},
  journal={The Journal of Clinical Pharmacology},
  year={2015},
  volume={55}
}
  • M. Géhin, D. Strasser, +4 authors P. Sidharta
  • Published 2015
  • Medicine
  • The Journal of Clinical Pharmacology
  • The chemoattractant receptor‐homologous molecule expressed on T‐helper 2 cells (CRTH2) is a G‐protein‐coupled receptor for prostaglandin D2, a key mediator in inflammatory disorders. In this randomized, double‐blind, placebo‐controlled study we investigated the single‐ and multiple‐dose tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) up to a dose of 800 mg once a day of ACT‐453859, a potent and selective CRTH2 antagonist. ACT‐453859 was moderately rapidly absorbed and followed a… CONTINUE READING
    15 Citations
    First‐in‐man study of ACT‐453859, a potent CRTH2 antagonist—Is the metabolite formation influenced by a polymorphic enzyme?
    • N. Srinivas
    • Medicine
    • Journal of clinical pharmacology
    • 2015
    Pharmacokinetic/Pharmacodynamic Modelling of Receptor Internalization with CRTH2 Antagonists to Optimize Dose Selection
    • 6
    Development of a decision-making biomarker for CRTH2 antagonism in clinical studies
    • 7
    CYP2C9 involvement in ACT‐453859 metabolism
    Prostaglandin D2 receptor antagonists in allergic disorders: safety, efficacy, and future perspectives
    • 18
    Investigational prostaglandin D2 receptor antagonists for airway inflammation
    • 17
    Impact of pharmacokinetic‐pharmacodynamic modelling in early clinical drug development
    • J. Dingemanse, Andreas Krause
    • Medicine
    • European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
    • 2017
    • 2

    References

    SHOWING 1-10 OF 28 REFERENCES
    CRTH2, an orphan receptor of T‐helper‐2‐cells, is expressed on basophils and eosinophils and responds to mast cell‐derived factor(s)
    • 275
    Inhibition of the asthmatic allergen challenge response by the CRTH2 antagonist OC000459
    • 81
    • PDF
    A randomized, double‐blind, placebo‐controlled study of the CRTH2 antagonist OC000459 in moderate persistent asthma
    • N. Barnes, I. Pavord, +9 authors C. Perkins
    • Medicine
    • Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
    • 2012
    • 186
    Anti‐eosinophil activity and clinical efficacy of the CRTH2 antagonist OC000459 in eosinophilic esophagitis
    • 156
    Clinical studies of the DP1 antagonist laropiprant in asthma and allergic rhinitis.
    • 47
    The roles of the prostaglandin D2 receptors DP1 and CRTH2 in promoting allergic responses
    • R. Pettipher
    • Medicine, Chemistry
    • British journal of pharmacology
    • 2008
    • 139
    • PDF
    Emerging roles of DP and CRTH2 in allergic inflammation.
    • 178