The gamma Delay statement

Phoenix Certara Forums PML School
1

Hi,

I am trying to build a population model with the gamma Delay statement to delay the absorption of the drug. I wrote a PML statement using the knowledge from certara phoenix assistance that described this concept. There is no warning but no iterations when I run the model, and the status is “in progress.” I am not sure if the statement needs a correction. The drug was administered orally, and previous population analysis shows two compartments model best describes its PK.
Can I please get help on this issue?

Here is the statement:

test(){
#deriv(A1 = - (Cl * C) + (Aa * Ka)- (Cl2 * (C - C2)))
#deriv(Aa = - (Aa * Ka))
delayInfCpt( A1, MeanDelayTime, ShapeParamMinusOne, out = - Cl*C - (Cl2 * (C - C2)),dist = Gamma )
deriv(A2 = (Cl2 * (C - C2)))
C = A1 / V
dosepoint(A1, idosevar = AaDose, infdosevar = AaInfDose, infratevar = AaInfRate)
C2 = A2 / V2
error(CEps = 1)
observe(CObs = C + CEps)
stparm(V = tvV * exp(nV))
stparm(Cl = tvCl * exp(nCl))
stparm(V2 = tvV2 * exp(nV2))
stparm(Cl2 = tvCl2 * exp(nCl2))
stparm(MeanDelayTime = tvMeanDelayTime * exp(nMeanDelayTime))
stparm(ShapeParamMinusOne =tvShapeParamMinusOne * exp(tvShapeParamMinusOne))
fixef(tvV = c(, 1, ))
fixef(tvCl = c(, 1, ))
fixef(tvV2 = c(, 1, ))
fixef(tvCl2 = c(, 1, ))
fixef(tvMeanDelayTime = c(, 1, ))
fixef(tvShapeParamMinusOne = c(, 2, ))
ranef(diag(nV, nCl, nMeanDelayTime, nV2, nCl2) = c(1, 1, 1, 1, 1))
}

Thanks !!

2

Hi David,

Found a few errors in your PML statement. You need to define the amount transferred from the gut to the central compartment. The statement should be

delayInfCpt(Aa, MTT, Ntr, out = -Aa * Ka, dist = Gamma)
deriv(A1 = - (Cl * C) + (Aa * Ka))
deriv(A2 = (Cl2*(C-C2)))

I have attached a project file (Sample) that could be of use to you. Please let us know if you need further assistance.

Thanks and regards

Mouli

01Gamma_DF.phxproj (1.49 MB)

3

Thanks, Mouli, for your answer and providing an example project.

I tried to use the same PML statement however both V2 and CL2 were not estimated well. I notice there are no iterations, and both are estimated with very high % CV (% in thousands).

I am wondering if we can use A1 with delay function for an oral drug instead of Aa.

I am not sure how to address this issue.

Thanks

2022-03-01 (6).png
2022-03-01 (6).png1200×437 240 KB

4

Hi David,

Sorry for the delayed response. Is it possible for you to share your project file? I would recommend not to use the forum. You could e-mail it to support@certara.com or please let me know a suitable time I can connect with you over Teams.

Thanks and regards

Chandramouli