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DDMODEL00000001: Friberg_2009_Schizophrenia_Prolactine

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Model comprised of files: Output_simulated_Prolactine_VPC.pdf, Model_Accomodation.txt, Executable_Friberg_2009_Schizophrenia_Prolactine.mdl, Friberg_2009_Schizophrenia_Prolactine_MAXEVAL0.lst, Command.txt, Simulated_Prolactine.csv, Executable_Friberg_2009_Schizophrenia_Prolactine.xml
PharmML (0.6.1)
  • An agonist-antagonist interaction model for prolactin release following risperidone and paliperidone treatment.
  • Friberg LE, Vermeulen AM, Petersson KJ, Karlsson MO
  • Clinical pharmacology and therapeutics, 4/2009, Volume 85, Issue 4, pages: 409-417
  • Department of Pharmaceutical Biosciences, Division of Pharmacokinetics and Drug Therapy, Uppsala University, Uppsala, Sweden. lena.friberg@farmbio.uu.se
  • A mechanistic pharmacokinetic/pharmacodynamic model is presented, characterizing the time course of prolactin in healthy as well as schizophrenic subjects following the administration of various doses and formulations of the antipsychotic drugs risperidone and paliperidone. Prolactin concentrations from nine studies (1,462 subjects) were analyzed in NONMEM. A competitive agonist-antagonist interaction model described the competition between these drugs and dopamine for the D(2) receptors that regulate prolactin release. Tolerance development was explained by a feedback loop with prolactin stimulating dopamine release, whereas models wherein tolerance is described in terms of depletion of a prolactin pool did not explain the data well. The diurnal prolactin rhythm was described by a two-period cosine function. Baseline prolactin was health-status dependent and higher in women than in men, although the drug-induced release was less than proportional to baseline. This quantitative mechanism-based model is the first to describe prolactin release in patients, and it confirms that paliperidone and risperidone have similar potencies for prolactin release.
Zinnia Parra-Guillen
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  • Model owner: Zinnia Parra-Guillen
  • Submitted: Sep 25, 2014 5:53:46 PM
  • Last Modified: May 24, 2016 11:53:14 AM
Revisions
  • Version: 15 public model Download this version
    • Submitted on: May 24, 2016 11:53:14 AM
    • Submitted by: Zinnia Parra-Guillen
    • With comment: Edited model metadata online.
  • Version: 6 public model Download this version
    • Submitted on: Dec 12, 2015 2:07:02 PM
    • Submitted by: Zinnia Parra-Guillen
    • With comment: Edited model metadata online.
  • Version: 2 public model Download this version
    • Submitted on: Sep 25, 2014 5:53:46 PM
    • Submitted by: Zinnia Parra-Guillen
    • With comment: Harmonised PharmML, MDL and NM-TRAN files according to established nomenclature
 
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