Examples - PML

PML examples

This chapter provides the following examples, modeled in both Phoenix and NONMEM.

Phenobarbital PML example: simple kinetics
Theophylline PML example: population modeling
User-defined logistic model PML example
Structural parameters and QRPEM PML example

The following section includes examples covering a range of functions.

Additional PML examples

Phenobarbital PML example

This example illustrates simple PK modeling for a one-compartment model with Cl (clearance) and V (volume) parameterization, and multiple doses per subject.

Data

The subject data are contained in an ASCII file (*.dat). The headers and the first subject data read as follows:

pheno.dat
## xid time dose wt apgr yobs
     1   0.0 25.0 1.4 7     .
     1   2.0   .   1.4 7   17.3
     1 12.5 3.5 1.4 7     .
     1 24.5 3.5 1.4 7     .
     1 37.0 3.5 1.4 7     .
     1 48.0 3.5 1.4 7     .
     1 60.5 3.5 1.4 7     .
     1 72.5 3.5 1.4 7     .
     1 85.3 3.5 1.4 7     .
     1 96.5 3.5 1.4 7     .
     1 108.5 3.5 1.4 7     .
     1 112.5   .   1.4 7   31.0

Column mappings

The ASCII file containing column mappings reads as follows.

colspheno.txt
id(xid)
time(time)
dose(a <- dose)
covr(wt <- wt)
obs(cObs <- yobs)

The model

The Phoenix model file reads as follows.

phenophxexam.mdl
# One compartment model with IV bolus dosing
  # Cl, V parameterization with differential equation
# formulation
Pheno(){
    dosepoint(a)
    covariate(wt) #wt is a covariate for Cl and V
    deriv(a=-a*Cl/V)
    c=a/V
    fixef(
       tvCl=c(0, 0.0001,)
       wtCl=c(0, 0.005,)
       tvV=c(0, 0.1,)
       wtV=c(0, 1,)
       )
    ranef(
       diag(nCl, nV)=c(0.1, 0.1,)
       )
    stparm(
       Cl=(tvCl+wtCl*wt)*exp(nCl)
       V=(tvV+wtV*wt)*exp(nV)
       )
#NONMEM initial estimate for sigma variance is 10
#Phoenix initial estimate represents a standard deviation
#rather than a variance, so the equivalent initial estimate is
#eps1=sqrt(10)=3.16
# error(eps1=3.16)
  # observe(cObs=c+eps1)
}

NONMEM control file

The equivalent model, written as a NONMEM control file (*.ctl), would read as follows.

$PROBLEM PHENOBARB SIMPLE MODEL
$INPUT ID TIME AMT WGT APGR DV
$DATA pheno.dat
  $SUBR ADVAN6
$MODEL COMP=(CENTRAL,DEFOBS,NOOFF)
$PK
    TVCL=THETA(1)+WGT*THETA(2)
    TVV=THETA(3)+WGT*THETA(4)
    CL=TVCL*EXP(ETA(1))
    V=TVV*EXP(ETA(2))
    S1=V
$THETA(0, 0.0001,)(0, 0.005,)(0, .1,)(0, 1,)
$OMEGA .1 .1
  $DES
    DADT(1)=-CL/V*A(1)
$ERROR
    Y=F+EPS(1)
$SIGMA 10
$ESTIMATION METHOD=1 PRINT=5 POSTHOC