DDMODEL00000040: Furosemide PK with transit compartment absorption

  public model
Short description:
PK model for furosemide from a study of clinically stable congestive heart failure patients by Frick et al.
Original code
  • Implementation of a transit compartment model for describing drug absorption in pharmacokinetic studies.
  • Savic RM, Jonker DM, Kerbusch T, Karlsson MO
  • Journal of pharmacokinetics and pharmacodynamics, 10/2007, Volume 34, Issue 5, pages: 711-726
  • Division of Pharmacokinetics and Drug Therapy, Department of Pharmaceutical Biosciences, Faculty of Pharmacy, Uppsala University, Uppsala 75234, Sweden. Rada.Savic@farmbio.uu.se
  • PURPOSE: To compare the performance of the standard lag time model (LAG model) with the performance of an analytical solution of the transit compartment model (TRANSIT model) in the evaluation of four pharmacokinetic studies with four different compounds. METHODS: The population pharmacokinetic analyses were performed using NONMEM on concentration-time data of glibenclamide, furosemide, amiloride, and moxonidine. In the TRANSIT model, the optimal number of transit compartments was estimated from the data. This was based on an analytical solution for the change in drug concentration arising from a series of transit compartments with the same first-order transfer rate between each compartment. Goodness-of-fit was assessed by the decrease in objective function value (OFV) and by inspection of diagnostic graphs. RESULTS: With the TRANSIT model, the OFV was significantly lower and the goodness-of-fit was markedly improved in the absorption phase compared with the LAG model for all drugs. The parameter estimates related to the absorption differed between the two models while the estimates of the pharmacokinetic disposition parameters were similar. CONCLUSION: Based on these results, the TRANSIT model is an attractive alternative for modeling drug absorption delay, especially when a LAG model poorly describes the drug absorption phase or is numerically unstable.
Rikard Nordgren
Context of model development: Mechanistic Understanding;
Long technical model description: Comparison of the perfomance of the standard lag time model with the performance of an analytical solution of the transit compartiment model in the evaluation of four PK studies. This model comes from one of these PK studies. The optimal number of transit compartments was estimated from the data.;
Model compliance with original publication: Yes;
Model implementation requiring submitter’s additional knowledge: No;
Modelling context description: Comparison of performance of standard lag time model with transit compartment model;
Modelling task in scope: estimation;
Nature of research: Early clinical development (Phases I and II);
Therapeutic/disease area: Cardiovascular;
Annotations are correct.
This model is not certified.
  • Model owner: Rikard Nordgren
  • Submitted: Dec 11, 2015 10:03:12 AM
  • Last Modified: Jun 3, 2016 8:20:35 AM
Revisions
  • Version: 15 public model Download this version
    • Submitted on: Jun 3, 2016 8:20:35 AM
    • Submitted by: Rikard Nordgren
    • With comment: Updated model annotations.
  • Version: 9 public model Download this version
    • Submitted on: Dec 11, 2015 12:49:10 PM
    • Submitted by: Rikard Nordgren
    • With comment: Edited model metadata online.
  • Version: 5 public model Download this version
    • Submitted on: Dec 11, 2015 10:03:12 AM
    • Submitted by: Rikard Nordgren
    • With comment: Edited model metadata online.
 
Help