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DDMODEL00000070: Population PK of edoxaban and main metabolite in renal impairment

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Short description:
Population Pharmacokinetics of Edoxaban and Its Main Metabolite in a Dedicated Renal Impairment Study. Model comprised of files: Command.txt, Output_simulated_original_run164.lst, Simulated_data.csv, Output_real_original_run164.lst, Executable_run164.mod
Original code
  • Population pharmacokinetics of edoxaban and its main metabolite in a dedicated renal impairment study.
  • Jönsson S, Simonsson US, Miller R, Karlsson MO
  • Journal of clinical pharmacology, 11/2015, Volume 55, Issue 11, pages: 1268-1279
  • Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
  • A model characterizing the population pharmacokinetics (PK) of edoxaban and its major metabolite, M4, following a single oral dose of 15?mg administered to subjects with varying kidney function was developed. Thirty-two subjects contributed with edoxaban plasma, edoxaban urine, and M4 plasma concentrations. Edoxaban urine concentrations allowed estimation of renal clearance, and high contribution of renal to total clearance enabled estimation of absolute oral bioavailability. A 2-compartment model with delayed absorption and elimination parameterized as renal clearance linearly related to creatinine clearance (CLcr ) and nonrenal clearance forming M4 described edoxaban PK. The PK of M4 was described with a 1-compartment model. For a typical subject (70?kg; CLcr , 100?mL/min) bioavailability, clearance, and central and peripheral volume of distribution for edoxaban was estimated to 72.3%, 21.0 L/h, 95.4 L, and 54.3 L, respectively. For both edoxaban and M4, the model predicted systemic exposure to increase 57.0%, 35.0%, and 11.6% in a subject having CLcr of 30, 50, and 80?mL/min, respectively, compared with a subject having a CLcr of 100?mL/min. Concentration ratios (M4 over edoxaban) were predicted to vary with time after dose, but with minor influence of kidney function and body weight. Results were in agreement with previous analyses.
Siv Jonsson
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  • Model owner: Siv Jonsson
  • Submitted: Dec 10, 2015 11:20:14 AM
  • Last Modified: Oct 6, 2016 2:56:08 PM
  • Version: 12 public model Download this version
    • Submitted on: Oct 6, 2016 2:56:08 PM
    • Submitted by: Siv Jonsson
    • With comment: Updated model annotations.
  • Version: 6 public model Download this version
    • Submitted on: Dec 10, 2015 11:20:14 AM
    • Submitted by: Siv Jonsson
    • With comment: Edited model metadata online.