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DDMODEL00000087: Benson 2014 - FAAH Inhibitors Systems Pharmacology Model for Pain

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A simulation systems pharmacology model developed for the human endocannabinoid system which aimed to optimize any further clinical development of FAAH inhibitors. This is a simulation model which has been curated by EMBL-EBI. The model is available in the BioModels Database and simulation can be performed (via the BioModels Online Simulation tool) at:
PharmML (0.6)
  • A systems pharmacology perspective on the clinical development of Fatty Acid amide hydrolase inhibitors for pain.
  • Benson N, Metelkin E, Demin O, Li GL, Nichols D, van der Graaf PH
  • CPT: pharmacometrics & systems pharmacology, 1/2014, Volume 3, pages: e91
  • Xenologiq, Canterbury, Kent, UK.
  • The level of the endocannabinoid anandamide is controlled by fatty acid amide hydrolase (FAAH). In 2011, PF-04457845, an irreversible inhibitor of FAAH, was progressed to phase II clinical trials for osteoarthritic pain. This article discusses a prospective, integrated systems pharmacology model evaluation of FAAH as a target for pain in humans, using physiologically based pharmacokinetic and systems biology approaches. The model integrated physiological compartments; endocannabinoid production, degradation, and disposition data; PF-04457845 pharmacokinetics and pharmacodynamics, and cannabinoid receptor CB1-binding kinetics. The modeling identified clear gaps in our understanding and highlighted key risks going forward, in particular relating to whether methods are in place to demonstrate target engagement and pharmacological effect. The value of this modeling exercise will be discussed in detail and in the context of the clinical phase II data, together with recommendations to enable optimal future evaluation of FAAH inhibitors.CPT: Pharmacometrics Systems Pharmacology (2014) 3, e91; doi:10.1038/psp.2013.72; published online 15 January 2014.
Phylinda Chan
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  • Model owner: Phylinda Chan
  • Submitted: Apr 7, 2016 4:48:48 PM
  • Last Modified: May 25, 2016 9:42:00 AM
  • Version: 6 public model Download this version
    • Submitted on: May 25, 2016 9:42:00 AM
    • Submitted by: Phylinda Chan
    • With comment: Updated model annotations.
  • Version: 4 public model Download this version
    • Submitted on: Apr 7, 2016 4:48:48 PM
    • Submitted by: Phylinda Chan
    • With comment: Edited model metadata online.