Pharmacokinetic/Pharmacodynamic Modelling of Receptor Internalization with CRTH2 Antagonists to Optimize Dose Selection

@article{Krause2015PharmacokineticPharmacodynamicMO,
  title={Pharmacokinetic/Pharmacodynamic Modelling of Receptor Internalization with CRTH2 Antagonists to Optimize Dose Selection},
  author={A. Krause and J. Zisowsky and D. Strasser and M. G{\'e}hin and Patricia N. Sidharta and Peter M. A. Groenen and J. Dingemanse},
  journal={Clinical Pharmacokinetics},
  year={2015},
  volume={55},
  pages={813-821}
}
  • A. Krause, J. Zisowsky, +4 authors J. Dingemanse
  • Published 2015
  • Biology, Medicine
  • Clinical Pharmacokinetics
    • Background and ObjectiveThe chemoattractant receptor-homologous molecule expressed on T helper-2 cells (CRTH2) is a G-protein-coupled receptor for prostaglandin D2 (PGD2), a key mediator in inflammatory disorders. Two selective and potent CRTH2 antagonists currently in clinical development, ACT-453859 and setipiprant, were compared with respect to their (predicted) clinical efficacy.MethodsPopulation pharmacokinetic (PK) and pharmacodynamic (PD) models were developed to characterize how plasma… CONTINUE READING
    View on Springer
    ncbi.nlm.nih.gov
    6 Citations
    Background Citations
    1
    6 Citations
    Citation Type

    Citation Type

    Pharmacokinetics, pharmacodynamics, tolerability and prediction of clinically effective dose of ACT‐774312: A novel CRTH2 antagonist
    • 2
    Biomarker‐guided clinical development of the first‐in‐class anti‐inflammatory FPR2/ALX agonist ACT‐389949
    • 14
    Efficacy and safety of the CRTh2 antagonist AZD1981 as add-on therapy to inhaled corticosteroids and long-acting β2-agonists in patients with atopic asthma
    • 9
    • PDF
    Efficacy and safety of setipiprant in seasonal allergic rhinitis: results from Phase 2 and Phase 3 randomized, double-blind, placebo- and active-referenced studies
    • 14
    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
    The Case for an Unblinded Modeler in Early Clinical Development

    References

    SHOWING 1-10 OF 21 REFERENCES
    Development of a decision-making biomarker for CRTH2 antagonism in clinical studies
    • 7
    Single‐ and multiple‐dose tolerability and pharmacokinetics of the CRTH2 antagonist setipiprant in healthy male subjects
    • 11
    A novel CRTH2 antagonist: Single‐ and multiple‐dose tolerability, pharmacokinetics, and pharmacodynamics of ACT‐453859 in healthy subjects
    • 15
    Setipiprant, a selective oral antagonist of human CRTH2: relative bioavailability of a capsule and a tablet formulation in healthy female and male subjects.
    • 6
    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
    Selective modulation of chemokinesis, degranulation, and apoptosis in eosinophils through the PGD2 receptors CRTH2 and DP.
    • 234
    Antagonism of the prostaglandin D2 receptors DP1 and CRTH2 as an approach to treat allergic diseases
    • 260
    Emerging roles of DP and CRTH2 in allergic inflammation.
    • 178
    Prostaglandin D2 Causes Preferential Induction of Proinflammatory Th2 Cytokine Production through an Action on Chemoattractant Receptor-Like Molecule Expressed on Th2 Cells
    • 205
    • PDF
    Effects of prostaglandin D2 on helper T cell functions.
    • 112