The Use of Physiology-Based Pharmacokinetic and Pharmacodynamic Modeling in the Discovery of the Dual Orexin Receptor Antagonist ACT-541468

@article{Treiber2017TheUO,
  title={The Use of Physiology-Based Pharmacokinetic and Pharmacodynamic Modeling in the Discovery of the Dual Orexin Receptor Antagonist ACT-541468},
  author={Alexander Treiber and Ruben de Kanter and Catherine Roch and John Gatfield and Christoph Boss and Markus von Raumer and Benno Schindelholz and Clemens Muehlan and Joop M A van Gerven and François Jenck},
  journal={The Journal of Pharmacology and Experimental Therapeutics},
  year={2017},
  volume={362},
  pages={489 - 503}
}
The identification of new sleep drugs poses particular challenges in drug discovery owing to disease-specific requirements such as rapid onset of action, sleep maintenance throughout major parts of the night, and absence of residual next-day effects. Robust tools to estimate drug levels in human brain are therefore key for a successful discovery program. Animal models constitute an appropriate choice for drugs without species differences in receptor pharmacology or pharmacokinetics. Translation… 

Nonclinical pharmacology of daridorexant: a new dual orexin receptor antagonist for the treatment of insomnia

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The dual orexin receptor antagonist daridorexant does not affect the pharmacokinetics of the BCRP substrate rosuvastatin

The results showed that concomitant administration of 25 mg daridorexant o.d. at steady state did not affect the exposure parameters of rosuvastatin in a relevant way, as indicated by the ratios of geometric means (GMRs) for both Cmax and AUC0‐∞.

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The use of daridorexant is considered safe, with no clinically significant side-effects including deprivation of next-morning residual effects, including pharmacodynamics, animal and human research, pharmacokinetics and safety.

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