Modelling of TNF-alpha concentrations upon LPS challenge in presence and absence of drug intervention

Phoenix Certara Forums Modelling and Simulation
1

Dear all,

Presently, I am working on a model to study the effect of the compound on the TNF-alpha concentrations upon LPS challenge. The model equations were based on a report titled " Modelling and design o challenge tests: Inflammatory and metabolic biomarker study examples", authored by Johan Gabrielsson et al.

I observed following results

  1. Identifiability issue of IC50.
  2. The IPRED values were close enough to the observation but the PRED values were increased upon increased upon the increase in dose.
    PK_PD LPS indiced TNF_alpha.phxproj (912 KB)

DV,IPRED and PRED vs Time1.tiff (401 KB)

gabrielsson2015 (1).pdf (1.53 MB)

2

Dear colleague

Where is your dose column? You mapped both id and treatment as id. You cannot do that.

Do you have cross over study here?

You need first to correct your data set and then I can certainly help you.

best Regards

Serge

3

The study was parallel design. The Dose is given in dosing column. I will try sorting the treatment and Subject mapped to ID.

4

Dear Serge,

The study was parallel design. Now I have sorted the treatments and the doses of the treatments were mentioned in doing tab. The analysis leads to following results

  1. The PRED and IPRED were close enough to the observations
  2. The IC50 value was unidentifiable with the treatments but surprisingly the IC50 value was calculated or placebo group where there was no compound intervention.

Kindly, help me if there was any mistake in the PML code.

PK_PD LPS indiced TNF_alpha.phxproj (2.5 MB)IPRED,PRED,DV vs Time1.tiff (1.06 MB)IPRED,PRED,DV vs Time2.tiff (392 KB)IPRED,PRED,DV vs Time3.tiff (391 KB)IPRED,PRED,DV vs Time4.tiff (165 KB)