NONMEM TO NLME transit compartments

Phoenix Certara Forums Modelling and Simulation
1

Hi

I am trying to use differential equations from a NONMEM published model on NLME but I cant figure it out “I am new in modeling”. The model is two compartment, first order of absorption with a chain of transit compartment.

Please find the attached document.

Thanks

transit Comp.pdf (53.3 KB)

2

We asked one of our developers to translate the NM-Tran code to PML, here is the code:

test(){

ntr is the structural parameter representing one less than the number of transit stages.

transit(Aa, mtt, ntr, max=50, out=-Aa*Ka)

deriv(A1 = Ka * Aa - Cl * C - Cl2 * (C - C2))

deriv(A2 = Cl2 * (C - C2))

dosepoint(Aa)

C = A1 / V

C2 = A2 / V2

error(CEps = 0.11) # sqrt(0.508876 )

covariate(ASSAY())

covariate(WT)

CRatio = ASSAY == 3? C*Ratio : C

CMultStdev = ASSAY == 3? PROP_ERR_DBS:PROP_ERR_Plasma

observe(CObs = CRatio + CEps * sqrt(1 + CRatio^2 * (CMultStdev/sigma())^2))

stparm(Ka = tvKa)

stparm(V = tvV * exp(nV))

stparm(V2 = tvV2 * exp(nV2) * (WT/70))

stparm(Cl = tvCl * exp(nCl) * (WT/70)**0.75)

stparm(Cl2 = tvCl2 * exp(nCl2))

stparm(mtt = tvmtt * exp(nmtt))

stparm(ntr = tvntr) # fixed

fixef(tvKa = c(, .55, ))

fixef(tvV = c(, 89, ))

fixef(tvV2 = c(, 234, ))

fixef(tvCl = c(, 7.6, ))

fixef(tvCl2 = c(, 19, ))

fixef(tvmtt = c(,1.05, ))

fixef(tvntr(freeze) =c(,6,))

fixef(Ratio = c(, 0.71, ))

define multiplicative sigmas

although we cannot code the correlation

fixef(PROP_ERR_Plasma = 0.09) #sqrt(0.00878848 )

fixef(PROP_ERR_DBS = 0.11) # sqrt(0.0124671)

ranef(diag(nV, nCl, nV2, nCl2, nmtt) = c(0.01, 0.064, 0.04, 0.17, 0.36))

}

Please try in Phoenix and let us know if you run into issues.

Bernd

3
4

Thanks Bernd for your help.

I think I need to add a function to describe enterohepatic recycling but I am not sure how to add it to PML

Here is the code “Drug is administered once” No dosing interval

test(){

ntr is the structural parameter representing one less than the number of transit stages.

transit(Aa, mtt, ntr, max=50, out=-Aa*Ka)

deriv(A1 = Ka * Aa - Cl * C - Cl2 * (C - C2))
deriv(A2 = Cl2 * (C - C2))
dosepoint(Aa)
C = A1 / V
C2 = A2 / V2
error(CEps = 0.1)
observe(CObs = C + CEps * sqrt(1 + C^2 * (CMultStdev/sigma())^2))
stparm(Ka = tvKa * exp(nKa))
stparm(V = tvV * exp(nV))
stparm(V2 = tvV2 * exp(nV2))
stparm(Cl = tvCl * exp(nCl))
stparm(Cl2 = tvCl2 * exp(nCl2))
stparm(mtt = tvmtt * exp(nmtt))
stparm(ntr = tvntr) # fixed
stparm(CMultStdev = tvCMultStdev)
fixef(tvKa = c(, 1, ))
fixef(tvV = c(, 162929.74, ))
fixef(tvV2 = c(, 625466, ))
fixef(tvCl = c(, 7243, ))
fixef(tvCl2 = c(, 7243, ))
fixef(tvmtt = c(,1.05, ))
fixef(tvntr(freeze) =c(,7,))
fixef(tvCMultStdev = c(,1, ))
ranef(diag(nV, nCl, nKa, nV2, nCl2, nmtt) = c(1, 1, 1, 1, 1, 1))
}

Thanks !!

5

You may know that we have covered quite a diverse set of scenarios as part of our PML School. There was one webinar around enterohepatic recirculation:

https://support.certara.com/forums/topic/990-lesson-7-enterohepatic-recirculation/

The entry covers all materials, slide deck, model and recorded webinar session.

Let me know if you need more.

Bernd

6

Hi amashehri,

The code that you attached is for single dose data or multiple dose data?

Thanks!

7

Hi

The code is for single dose data