3 replies to this topic

[Davidq8]

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 !!

[cradhakr]

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

 

 

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 !!

 

 

Attached Files

•  01Gamma_DF.phxproj   1.49MB   146 downloads

[Davidq8]

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 

Attached Thumbnails

• 

Edited by Davidq8, 01 March 2022 - 09:53 PM.

[cradhakr]

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