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Modelling time varying covariates Using Monolix suite 2018R2


#1

Dear all,
please let me know if you can help me with this code in mlxtran in monolix,

Now i’m working on oral 1 compartment Pk model for tacrolimus, I’ve covariates that are time- varying,
so according to their manual ,they have to be defiend as regessors in the structural model
I did already every single covariate as a continous/ discrete groups and the code run okey,
My question is:
How can I add different regessors with different model together so i can build the full model???

I’ll post some example from my data and equations
1- I’ve Post-operative days as discret time varying covariate on Clearance
i transformed the PODs into groups and i applied those equations in the mlxtran file:

DESCRIPTION:
The administration is extravascular with a first order absorption (rate constant ka).
The PK model has one compartment (volume V) and a linear elimination (clearance Cl).

[LONGITUDINAL]
input = {ka, V, Cl,POD,beta1,beta2,beta3,beta4}
POD={use=regressor}

EQUATION:
if POD == 1
ClwithPOD = Cl
elseif POD == 2
ClwithPOD = Cl * (1+beta1)
elseif POD == 3
ClwithPOD = Cl * (1+beta2)
elseif POD == 4
ClwithPOD = Cl * (1+beta3)
else
ClwithPOD = Cl * (1+beta4)
end

; PK model definition
Cc = pkmodel(ka, V, Cl=ClwithPOD)

OUTPUT:
output = Cc
table = ClwithPOD

2- I’ve ALT levels as a continuous time-varying covariate on Clearance
I applied those equations in the mlxtran file:
[LONGITUDINAL]
input = {ka, V, Cl,ALT,beta1}
ALT={use=regressor}

EQUATION:
ClwithALT=Cl + (beta1 * ALT)
; PK model definition
Cc = pkmodel(ka, V, Cl=ClwithALT)

OUTPUT:
output = Cc
table=ClwithALT

now both of them and other different covariate were significant as single forward inclusion,
how can i combine all of them together???

Thnaks in advance