6 replies to this topic

[Davidq8]

Hi, I am building a population Pk model for an oral drug. The plasma concentration-time curve suggests two compartments for the Structural model. Adding a Tlag function to delay absorption has improved the fit; however, I believe modeling the absorption process using transit compartments models will improve the general fitting of the model. I need help to write the codes for the Transit compartments for extravascular administration with two compartments. I really appreciate help and suggestions.  

 

Thanks  

[kniefort]

 

Hi, I am building a population Pk model for an oral drug. The plasma concentration-time curve suggests two compartments for the Structural model. Adding a Tlag function to delay absorption has improved the fit; however, I believe modeling the absorption process using transit compartments models will improve the general fitting of the model. I need help to write the codes for the Transit compartments for extravascular administration with two compartments. I really appreciate help and suggestions.  

 

Thanks  

 

 

Have you considered using a delay function instead?

 

https://onlinehelp.c...=delay&rhsyns=

[bwendt@certara.com]

You did not provide an example Phoenix project file. Let me start with a standard 2-comp oral model in PML:

 

___________________________________

test(){
 deriv(A1 = - (Cl * C) + (Aa * Ka)- (Cl2 * (C - C2)))
 deriv(Aa = - (Aa * Ka))
 deriv(A2 = (Cl2 * (C - C2)))
 C = A1 / V
 dosepoint(Aa, 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(Ka = tvKa * exp(nKa))
 stparm(V2 = tvV2 * exp(nV2))
 stparm(Cl2 = tvCl2 * exp(nCl2))
 fixef(tvV = c(, 1, ))
 fixef(tvCl = c(, 1, ))
 fixef(tvKa = c(, 1, ))
 fixef(tvV2 = c(, 1, ))
 fixef(tvCl2 = c(, 1, ))
 ranef(diag(nV, nCl, nKa, nV2, nCl2) = c(1, 1, 1, 1, 1))
}

_________________________________________________

 

For a transit compartment, just add a transit statement:

--------------------------------------------------------------------------------------

test(){
 #deriv(Aa = - (Aa * Ka))
 transit(Aa, mtt, ntr, max=50, out=-Aa*Ka)
 deriv(A1 = - (Cl * C) + (Aa * Ka)- (Cl2 * (C - C2)))
 deriv(A2 = (Cl2 * (C - C2)))
 C = A1 / V
 dosepoint(Aa, 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(Ka = tvKa * exp(nKa))
 stparm(V2 = tvV2 * exp(nV2))
 stparm(Cl2 = tvCl2 * exp(nCl2))
 stparm(mtt = tvmtt)
 stparm(ntr = tvntr)
 fixef(tvV = c(, 1, ))
 fixef(tvCl = c(, 1, ))
 fixef(tvKa = c(, 1, ))
 fixef(tvV2 = c(, 1, ))
 fixef(tvCl2 = c(, 1, ))
 fixef(tvmtt = c(,1,))
 fixef(tvntr= c(,1,))
 ranef(diag(nV, nCl, nKa, nV2, nCl2) = c(1, 1, 1, 1, 1))
}

----------------------------------------------------------------------------

 

For the delay-function that Keith suggested, a few additional changes need to be done:

 

-----------------------------------------------------------------------------

test(){
 #deriv(A1 = - (Cl * C) + (Aa * Ka)- (Cl2 * (C - C2)))
 #deriv(Aa = - (Aa * Ka))
 delayInfCpt( A1, mtt, ntr, out = - Cl*C - (Cl2 * (C - C2)))
 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(Ka = tvKa * exp(nKa))
 stparm(V2 = tvV2 * exp(nV2))
 stparm(Cl2 = tvCl2 * exp(nCl2))
 stparm(mtt = tvmtt)
 stparm(ntr = tvntr)
 fixef(tvV = c(, 1, ))
 fixef(tvCl = c(, 1, ))
 #fixef(tvKa = c(, 1, ))
 fixef(tvV2 = c(, 1, ))
 fixef(tvCl2 = c(, 1, ))
 fixef(tvmtt = c(,5,))
 fixef(tvntr= c(,10,))
 ranef(diag(nV, nCl, nKa, nV2, nCl2) = c(1, 1, 1, 1, 1))
}

-----------------------------------------------------------------------------

 

Please let us know if you run into issues.

 

Bernd

[Simon Davis]

the online help has more background about PML syntaxt if you have not found this yet; https://onlinehelp.c...ment_models.htm

[Davidq8]

Have you considered using a delay function instead?

 

https://onlinehelp.c...=delay&rhsyns=

Thanks, kniefort for your suggestion! I will try it.

Edited by Davidq8, 11 February 2022 - 07:28 PM.

[Davidq8]

You did not provide an example Phoenix project file. Let me start with a standard 2-comp oral model in PML:

 

___________________________________

test(){
 deriv(A1 = - (Cl * C) + (Aa * Ka)- (Cl2 * (C - C2)))
 deriv(Aa = - (Aa * Ka))
 deriv(A2 = (Cl2 * (C - C2)))
 C = A1 / V
 dosepoint(Aa, 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(Ka = tvKa * exp(nKa))
 stparm(V2 = tvV2 * exp(nV2))
 stparm(Cl2 = tvCl2 * exp(nCl2))
 fixef(tvV = c(, 1, ))
 fixef(tvCl = c(, 1, ))
 fixef(tvKa = c(, 1, ))
 fixef(tvV2 = c(, 1, ))
 fixef(tvCl2 = c(, 1, ))
 ranef(diag(nV, nCl, nKa, nV2, nCl2) = c(1, 1, 1, 1, 1))
}

_________________________________________________

 

For a transit compartment, just add a transit statement:

--------------------------------------------------------------------------------------

test(){
 #deriv(Aa = - (Aa * Ka))
 transit(Aa, mtt, ntr, max=50, out=-Aa*Ka)
 deriv(A1 = - (Cl * C) + (Aa * Ka)- (Cl2 * (C - C2)))
 deriv(A2 = (Cl2 * (C - C2)))
 C = A1 / V
 dosepoint(Aa, 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(Ka = tvKa * exp(nKa))
 stparm(V2 = tvV2 * exp(nV2))
 stparm(Cl2 = tvCl2 * exp(nCl2))
 stparm(mtt = tvmtt)
 stparm(ntr = tvntr)
 fixef(tvV = c(, 1, ))
 fixef(tvCl = c(, 1, ))
 fixef(tvKa = c(, 1, ))
 fixef(tvV2 = c(, 1, ))
 fixef(tvCl2 = c(, 1, ))
 fixef(tvmtt = c(,1,))
 fixef(tvntr= c(,1,))
 ranef(diag(nV, nCl, nKa, nV2, nCl2) = c(1, 1, 1, 1, 1))
}

----------------------------------------------------------------------------

 

For the delay-function that Keith suggested, a few additional changes need to be done:

 

-----------------------------------------------------------------------------

test(){
 #deriv(A1 = - (Cl * C) + (Aa * Ka)- (Cl2 * (C - C2)))
 #deriv(Aa = - (Aa * Ka))
 delayInfCpt( A1, mtt, ntr, out = - Cl*C - (Cl2 * (C - C2)))
 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(Ka = tvKa * exp(nKa))
 stparm(V2 = tvV2 * exp(nV2))
 stparm(Cl2 = tvCl2 * exp(nCl2))
 stparm(mtt = tvmtt)
 stparm(ntr = tvntr)
 fixef(tvV = c(, 1, ))
 fixef(tvCl = c(, 1, ))
 #fixef(tvKa = c(, 1, ))
 fixef(tvV2 = c(, 1, ))
 fixef(tvCl2 = c(, 1, ))
 fixef(tvmtt = c(,5,))
 fixef(tvntr= c(,10,))
 ranef(diag(nV, nCl, nKa, nV2, nCl2) = c(1, 1, 1, 1, 1))
}

-----------------------------------------------------------------------------

 

Please let us know if you run into issues.

 

Bernd

Thanks, Bernd, for providing codes for both models, I really appreciate your help!!

[Davidq8]

the online help has more background about PML syntaxt if you have not found this yet; https://onlinehelp.c...ment_models.htm

Thanks Simon for sharing the link!