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DDMODEL00000076: Yan_2011_EPO_biosimilar_PKPD

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Short description:
Model comprised of files: Output_real_EPO.lst, Simulated_EPO_dataset.csv, Executable_simulated_EPO_dataset.ctl, Output_simulated_ EPO_dataset.lst, Command.txt
Original code
  • Population pharmacokinetic and pharmacodynamic model-based comparability assessment of a recombinant human Epoetin Alfa and the Biosimilar HX575.
  • Lowe PJ, Berghout A, Balser S, Krzyzanski W, Yan X, Fink M
  • Journal of clinical pharmacology, 11/2012, Volume 52, Issue 11, pages: 1624-1644
  • (1) Department of Pharmaceutical Sciences, State University of New York at Buffalo, (2) Modeling and Simulation, Novartis Pharma AG (3) Sandoz Biopharmaceuticals
  • The aim of this study was to develop an integrated pharmacokinetic and pharmacodynamic (PK/PD) model and assess the comparability between epoetin alfa HEXAL/Binocrit (HX575) and a comparator epoetin alfa by a model-based approach. PK/PD data-including serum drug concentrations, reticulocyte counts, red blood cells, and hemoglobin levels-were obtained from 2 clinical studies. In sum, 149 healthy men received multiple intravenous or subcutaneous doses of HX575 (100 IU/kg) and the comparator 3 times a week for 4 weeks. A population model based on pharmacodynamics-mediated drug disposition and cell maturation processes was used to characterize the PK/PD data for the 2 drugs. Simulations showed that due to target amount changes, total clearance may increase up to 2.4-fold as compared with the baseline. Further simulations suggested that once-weekly and thrice-weekly subcutaneous dosing regimens would result in similar efficacy. The findings from the model-based analysis were consistent with previous results using the standard noncompartmental approach demonstrating PK/PD comparability between HX575 and comparator. However, due to complexity of the PK/PD model, control of random effects was not straightforward. Whereas population PK/PD model-based analyses are suited for studying complex biological systems, such models have their limitations (statistical), and their comparability results should be interpreted carefully.
Celine Sarr
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  • Model owner: Celine Sarr
  • Submitted: Dec 9, 2015 9:58:13 AM
  • Last Modified: May 20, 2016 5:40:57 PM
  • Version: 19 public model Download this version
    • Submitted on: May 20, 2016 5:40:57 PM
    • Submitted by: Celine Sarr
    • With comment: Updated model annotations.
  • Version: 4 public model Download this version
    • Submitted on: Dec 9, 2015 9:58:13 AM
    • Submitted by: Celine Sarr
    • With comment: Edited model metadata online.