DDMODEL00000050: Rifampicin PKPD model in a tuberculosis mouse using Multistate Tuberculosis Pharmacometric Model

  public model
Short description:
Model comprised of files: simulated_data_rif_pkpd_acute_mouse.csv, command_target.txt, Output_simulated_rif_pkpd_acute_mouse_output_original.lst, Executable_rif_pkpd_acute_mouse.mod
Original code
  • The Multistate Tuberculosis Pharmacometric Model – A Semi Mechanistic Pharmacokinetic-Pharmacodynamic Model for Studying Drug Effects in a Tuberculosis Acute Mouse Model
  • Chunli Chen, Fatima Ortega, Joaquin Rullas-Trincado, Raquel Moreno, Inigo Angulo, Santiago Ferrer, Ulrika SH Simonsson
  • the Population Approach Group in Europe, 6/2013
  • Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden
  • The effect of rifampicin on Mycobacterium tuberculosis (M. tuberculosis) in vitro has been described using the Multistate Tuberculosis Pharmacometric Model, a pharmacokinetic -pharmacodynamic disease model approach. The aim of this work was to investigate if the approach could be used in order to describe rifampicin treatment response in a tuberculosis acute mouse model. A group of C57BL/6 mice (n=60) were intratracheally infected with M. tuberculosis H37Rv at Day 0. Rifampicin (1, 3, 9, 26 or 98 mg/kg) was administered daily during Days 1 to 8. Fifteen mice received no treatment. Mice were sacrificed at Day 1, 9 and 18 in un-treated group and at Day 9 only in treated group. An additional twenty mice were given 30 mg/kg rifampicin orally once daily for up to 9 days. At Days 2, 3, 4 and 9, five mice were sacrificed at each occasion. The Multistate Tuberculosis Pharmacometric Model, including differential equations for different sub-states of M. tuberculosis was linked to the rifampicin pharmacokineticmodel (Chen C, Ortega F, Alameda L, Ferrer S and Simonsson USH, submitted for publication) in order to describe the change in colony forming units (cfu) in lungs over time using NONMEM. The M3 method was used in order to account for data below low limit of quantification (LLQ). In summary, the Multistate Tuberculosis Pharmacometric Model captured well the bi-exponential decline in cfu and was able to link drug effects in a mechanistic way to different sub-states of M. tuberculosis.
Chunli Chen
Annotations have not been checked.
This model is not certified.
  • Model owner: Chunli Chen
  • Submitted: Dec 11, 2015 3:45:23 PM
  • Last Modified: Dec 11, 2015 3:45:23 PM
  • Version: 13 public model Download this version
    • Submitted on: Dec 11, 2015 3:45:23 PM
    • Submitted by: Chunli Chen
    • With comment: Edited model metadata online.