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DDMODEL00000003: Hamren_2008_diabetes_tesaglitazar

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Short description:
Population PK/PD model describing the interplay between tesaglitazar and fasting plasma glucose, hemoglobin, and glycosylated hemoglobin in type 2 diabetic patients.
PharmML (0.6.1)
  • Models for plasma glucose, HbA1c, and hemoglobin interrelationships in patients with type 2 diabetes following tesaglitazar treatment.
  • Hamrén B, Björk E, Sunzel M, Karlsson M
  • Clinical pharmacology and therapeutics, 8/2008, Volume 84, Issue 2, pages: 228-235
  • Department of Medical Science, Clinical Pharmacology, AstraZeneca R&D Mölndal, Mölndal, Sweden. bengt.hamren@astrazeneca.com
  • Pharmacokinetic (PK) pharmacodynamic (PD) modeling was applied to understand and quantitate the interplay between tesaglitazar (a peroxisome proliferator-activated receptor alpha/gamma agonist) exposure, fasting plasma glucose (FPG), hemoglobin (Hb), and glycosylated hemoglobin (HbA1c) in type 2 diabetic patients. Data originated from a 12-week dose-ranging study with tesaglitazar. The primary objective was to develop a mechanism-based PD model for the FPG-HbA1c relationship. The secondary objective was to investigate possible mechanisms for the tesaglitazar effect on Hb. Following initiation of tesaglitazar therapy, time to new FPG steady state was approximately 9 weeks, and tesaglitazar potency in females was twice that in males. The model included aging of red blood cells (RBCs) using a transit compartment approach. The RBC life span was estimated to 135 days. The transformation from RBC to HbA1c was modeled as an FPG-dependent process. The model indicated that the tesaglitazar effect on Hb was caused by hemodilution of RBCs.
Paolo Magni
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  • Model owner: Paolo Magni
  • Submitted: Dec 10, 2015 10:16:55 AM
  • Last Modified: Oct 10, 2016 9:31:51 PM
Revisions
  • Version: 10 public model Download this version
    • Submitted on: Oct 10, 2016 9:31:51 PM
    • Submitted by: Paolo Magni
    • With comment: Update MDL syntax to the version 1.0 and R script to SEE version 2.0.0. Code automatically generated for NONMEM and MONOLIX
  • Version: 9 public model Download this version
    • Submitted on: Jun 2, 2016 8:37:50 PM
    • Submitted by: Paolo Magni
    • With comment: Updated model annotations.
  • Version: 6 public model Download this version
    • Submitted on: Dec 11, 2015 7:47:09 PM
    • Submitted by: Paolo Magni
    • With comment: Edited model metadata online.
  • Version: 4 public model Download this version
    • Submitted on: Dec 10, 2015 10:16:55 AM
    • Submitted by: Paolo Magni
    • With comment: Updated simulated data set
 
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