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