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

  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},
  • 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
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