Fixed Baseline for PK/PD Model

Phoenix Certara Forums Modelling and Simulation
1

Hello,

Can somebody help me edit the code below to fix baseline to 100.

Thanks Greatly!

test(){
deriv(A1 = (Aa * Ka)- (Q1 * (C - C4))- (Q2 * C)- (Q3 * C))
deriv(Aa = - (Aa * Ka))
deriv(A4 = (Q1 * (C - C4)))
deriv(A3 = (Q3 * C)- (CL3 * C3))
deriv(A2 = (Q2 * C)- (CL2 * C2))
urinecpt(A0 = (CL3 * C3))
urinecpt(A0 = (CL2 * C2))
C = A1 / V
dosepoint(Aa, idosevar = AaDose, infdosevar = AaInfDose, infratevar = AaInfRate)
C4 = A4 / V4
error(CEps = 0.568143)
observe(CPlasma = C * (1 + CEps))
C3 = A3 / V3
C2 = A2 / V2
error(CEps = 1)
observe(CKidney = C3 * (1 + CEps))
error(CEps = 1)
observe(CLiver = C2 * (1 + CEps))
E = E0 * (1 - C2^Gam / (EC50^Gam + C2^Gam))
error(CEps = 1)
observe(EObs = E + CEps)
stparm(V = tvV * exp(nV))
stparm(Ka = tvKa * exp(nKa))
stparm(V4 = tvV4 * exp(nV4))
stparm(Q1 = tvQ1 * exp(nQ1))
stparm(V3 = tvV3 * exp(nV3))
stparm(V2 = tvV2 * exp(nV2))
stparm(Q2 = tvQ2 * exp(nQ2))
stparm(Q3 = tvQ3 * exp(nQ3))
stparm(CL3 = tvCL3 * exp(nCL3))
stparm(CL2 = tvCL2 * exp(nCL2))
stparm(EC50 = tvEC50 * exp(nEC50))
stparm(E0 = tvE0 * exp(nE0))
stparm(Gam = tvGam * exp(nGam))
fcovariate(Grp)
fixef(tvV = c(, 574.645, ))
fixef(tvKa = c(, 4.06913, ))
fixef(tvV4 = c(, 4912.16, ))
fixef(tvQ1 = c(, 34.632, ))
fixef(tvV3 = c(, 87.0643, ))
fixef(tvV2 = c(, 5.25679, ))
fixef(tvQ2 = c(, 28.6318, ))
fixef(tvQ3 = c(, 251.738, ))
fixef(tvCL3 = c(, 0.119304, ))
fixef(tvCL2 = c(, 0.0125202, ))
fixef(tvEC50 = c(, 5.88945, ))
fixef(tvE0 = c(, 100, ))
fixef(tvGam = c(, 0.981281, ))
ranef(diag(nV2, nV3, nV, nKa, nV4, nQ1, nQ2, nQ3, nCL3, nCL2, nEC50, nE0, nGam) = c(0.097440168, 0.44811222, 0.12461778, 0.44013485, 2.7900362E-05, 0.10684659, 0.0017777742, 0.096972774, 0.10017247, 0.021310942, 1, 1, 1))
}

2

Sorry I figured this out myself , just frooze it in the model

fixef(tvE0(freeze) = c(, 100, ))

3

I’m glad you figured it out. One of the best ways to learn PML code is to create a new model (any one will do) and then change settings in the GUI and see how the text PML code changes. Then apply those same changes to your original model.

4

Hi,
you code fixes the population level value. On the other hand the individual values E0 will deviate from 100 with the specified distribution

stparm(E0 = tvE0 * exp(nE0))
fixef(tvE0(freeze) = c(, 100, ))
ranef(diag(nV2, nV3, nV, nKa, nV4, nQ1, nQ2, nQ3, nCL3, nCL2, nEC50, nE0, nGam) = c(0.097440168, 0.44811222, 0.12461778, 0.44013485, 2.7900362E-05, 0.10684659, 0.0017777742, 0.096972774, 0.10017247, 0.021310942, 1, 1, 1)

so here the initial estimate of nE0 is 1 and depending on how it will be estimated individual values will be

100 * exp ( random variable with mean zero and variance nE0 here the initial is 1)

if you issue this command in R

100*exp(rnorm(5,0,1)) # 5 random samples from a normal distribution with mean 0 and sd of 1))
[1] 79.97296 114.06433 70.29925 28.08607 41.22702

so on average and with enough sample size you will get a typical value of 100 but individual values might deviate substantially from 100

if you want all subjects to start at a fixed value of 100 also remove nE0.

Samer