2 replies to this topic

[Davidq8]

Hi, I am working on a population Pk model focusing on the absorption phase of an oral drug. I found this study with an interesting absorption scenario (please see figure):

After oral administration, the drug goes to an absorption compartment with two depots (depots 1 and 2). Then the drug moves from depot 1 to 2 with Ka1 and Tlag and finally from depot2 to the central compartment with Ka2. So based on this scenario, we have two first-order absorption rates. My question can I get help on how to write PML lines that describe this process.

I am also attaching the article for your reference.

Attached Thumbnails

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Attached Files

•  pharmaceutics-12-00374-v234125.pdf   2.08MB   340 downloads

[cradhakr]

Hi David,

 

Thanks for sharing the publication. I have attached the project file (simulation) based on the estimates from this paper using a graphical model

 

The PML code for this model is:

 

test(){

deriv(A1 = - (Cl * C) + (A2 * Ka2))

urinecpt(A0 = (Cl * C))

deriv(Aa = - (Aa * Ka1))

deriv(A2 = (Aa * Ka1)- (A2 * Ka2))

C = A1 / V

dosepoint(Aa, tlag = (Tlag), idosevar = AaDose, infdosevar = AaInfDose, infratevar = AaInfRate)

error(CEps = 0.357)

observe(CObs = C * exp(CEps))

stparm(V = tvV * (1+(TotalProtein-7.6)*dVdTotalProtein) * exp(nV))

stparm(Cl = tvCl * (1+(TotalProtein-7.6)*dCldTotalProtein) * exp(nCl))

stparm(Tlag = tvTlag * exp(nTlag))

stparm(Ka1 = tvKa1 * exp(nKa1))

stparm(Ka2 = tvKa2 * exp(nKa2))

fcovariate(TotalProtein)

fixef(tvV = c(, 1717060.491, ))

fixef(tvCl = c(, 447163.154, ))

fixef(tvTlag = c(, 0.196, ))

fixef(tvKa1 = c(, 3.187, ))

fixef(tvKa2 = c(, 3.183, ))

fixef(dVdTotalProtein(enable=c(0)) = c(, -1.049, ))

fixef(dCldTotalProtein(enable=c(1)) = c(, -0.804, ))

ranef(diag(nV, nCl, nTlag, nKa2, nKa1) = c(0.326, 0.16, 0.107, 0.557, 0.556))

}

 

 

Simulation-based on this model

 

 

Please let me know if you need further assistance. Thanks and regards

 

Mouli

Attached Files

•  Simulation01.phxproj   376.21KB   131 downloads

[Davidq8]

Thank you Mouli for your time providing me a clear explanation on how to do this scenario using PML.

 

I have another question, I have been working on different absorption scenarios recently and I came up with this model :

 

cfMicro(A1, Cl / V, Cl2 / V, Cl2 / V2, first = (Aa = Ka))

dosepoint(Aa, tlag = Tlag,duration = TK0 )

C = A1 / V

 

The fit I got was a very good one but at that time I was thinking how to describe it. After reading the above article I came up with this possible explanation for this scenario:

 

After dosing the drug moves from depot 1 to 2 by zero order absorption rate (TK0) and Tlag and then from depot 2 to central compartment by first order absorption (Ka).

 

I am not sure if this explanation is quite accurate ?

 

Thanks