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Libraries of models


Objectives: learn how to use the Monolix libraries of PKPD models and create your own libraries.


Projects: warfarinPKlibrary_project, PDsim_project, warfarinPKPDlibrary_project, warfarinPKPDelibrary_project, hcv_project


The PK library

  • theophylline_project (data = ‘theophylline_data.txt’ , model=’lib:oral1_1cpt_kaVCl.txt’)

A one compartment PK model for oral administration with first order absorption and linear elimination is used for fitting the theophylline data. The model oral1_1cpt_TlagkaVCl from the PK library is used:


Click on the button Model file to select or modify a model. Then, select the PK library from the menu Monolix


Click on the Edit button to edit the model:

[LONGITUDINAL]
input = {ka, V, Cl}
EQUATION:
Cc = pkmodel(ka, V, Cl)
OUTPUT:
output = Cc

The name of the PK model appears in the section [LONGITUDINAL] of the project file

<MODEL>
[INDIVIDUAL]
input = {ka_pop, omega_ka, V_pop, omega_V, Cl_pop, omega_Cl}
DEFINITION:
ka = {distribution=lognormal, typical=ka_pop, sd=omega_ka}
V = {distribution=lognormal, typical=V_pop, sd=omega_V}
Cl = {distribution=lognormal, typical=Cl_pop, sd=omega_Cl}
[LONGITUDINAL]
input = a
file = 'lib:oral1_1cpt_kaVCl.txt'
DEFINITION:
concentration = {distribution=normal, prediction=Cc, errorModel=constant(a)}

The PD library

  • PDsim_project (data = ‘PDsim_data.txt’ , model=’lib:immed_Emax_const.txt’)

An Emax PD model with constant baseline is used for this project.

Link a PK model and a PD model

  • warfarinPKlibrary_project (data = ‘warfarin_data.txt’ , model=’lib:oral1_1cpt_TlagkaVCl.txt’)

We first fit the PK data of the warfarin data using a model from the PK library

  • warfarinPKPDlibrary_project (data = ‘warfarin_data.txt’ , model= {‘lib:oral1_1cpt_TlagkaVCl.txt’, ‘lib:immed_Imax_const.txt’})

To fit simultaneously the PK and the PD warfarin data, we need to link the PK model with a PD model. Click on the +

and select a model from the PD library. We will use here the immediate response model immed_Imax_const from the Monolix PD library

[LONGITUDINAL]
input = {Cc, Imax, IC50, S0}
Cc = {use=regressor}
EQUATION:
E = S0*(1 - Imax*Cc/(Cc+IC50))
OUTPUT:
output = E

Two models then appear in the list of model files:

Link a PK model and a PD model with an effect compartment

  • warfarinPKPDelibrary_project (data = ‘warfarin_data.txt’ , model= {‘lib:oral1_1cpt_TlagkaVClke0.txt’, ‘lib:immed_Imax_const_Ce.txt’})

Inserting an effect compartment is made possible by using the PKe library

and the PDe library

Then, these 2 models are linked for fitting simultaneously the PK and the PD warfarin data.

Create and use your own libraries

  • 8.case_studies/hcv_project (data = ‘hcv_data.txt’ , model=’VKlibrary/hcvNeumann98_model.txt’)

You can use the mlxEditor, or any other text editor, for creating new models and new libraries of models. A basic library which includes several viral kinetics model is available in 8.case_studies/model. Click on Other list for selecting this library or any other existing library of models.