Re: Modeling compartment initial conditinns using ETA()= EPS(1) and CPZEROmeasure
Kazimierz,
You dont give any reason for "I need a method to force using EPS(1) intead
ETA() for estimating initial steady-state compartment concentration for $DES".
I am guessing you are trying to estimate the population initial steady state
conc with a random effect describing the between subject variability and also
want to describe the residual error for the observed concs. Because there is
only one initial steady state conc per subject then you can do this with ETA.
Just because you are trying to predict a concentration it does not mean you
need to use EPS. The SS conc is a subject specific parameter. It varies from
subject to subject. In addition you can expect a further residual random effect
due to measurement error etc.
$THETA 100 ; POP_SS_CONC Population estimate of SS conc
$THETA (0,0.1,) ; SSCONC_SD StdDev of random effect on SS conc parameter
$THETA (0,0.01,) ; OBS_SD StdDev of random effect on observed concs
$OMEGA 1 FIX ; Unit variance for SS conc
$SIGMA 1 FIX ; Unit variance for observed concs
$PK
RUVCSS=THETA(2) ; StdDev of random effect on SS conc parameter
SSCONC=THETA(1) + RUVCSS*ETA(1) ; individual prediction of parameter describing
SS conc
; you can use SSCONC to initialize a DE compartment e.g like this with NMVI
A_0(1)=SSCONC
$DES
DADT(1)= diff eqn for the conc that starts at SSCONC
$ERROR
RUVOBS=THETA(3) ; StdDev of random effect on observed concs
CONC=A(1); predict the observed conc (which may be a measurement of the SS conc)
Y=CONC + RUVOBS*EPS(1) ; prediction of conc with random effect for observation
Nick
"Kazimierz H. Kozlowski" wrote:
>
> Dear NM-Users,
>
> I need a method to force using EPS(1) intead ETA() for estimating
> initial steady-state compartment concentration for $DES.
> Pre-dose TIME for SS-ending is known. I used the following
> abbreviated codes in ERROR, and NONMEM act well, but predics individual
> regression stricted to measure CPZERO.
>
> sincerely
> Kazimierz H. Kozlowski
>
> $DES
> DADT(1)=-K*A(1)-K12*A(1)+K21*A(2)
> DADT(2)=K12*A(1)-K21*A(2)
> $ERROR
> COM(1)=ERR(1) ;QUESTION: WHY ERR(1)=0.0 in write-file and in
> TABLE?
> WRITE (50,*) COM(1),ERR(1),ICALL,COMACT ; COM(1)=0, ICALL=2 always
> FZ=THETA(10)*ERR(1)*THETA(10)*ERR(1) ;FZ=ERR**2
> FZ1=1.0-FZ*THETA(9)*THETA(9) ;FZ1=1-ERR*2*TH9*2
> EXP1=(K-BETA)*EXP(-ALPHA*(IAGE+TIME))
> EXP2=(ALPHA-K)*EXP(-BETA*(IAGE+TIME))
> EXP3=ALPHA*EXP(-BETA*(IAGE+TIME))
> EXP4=BETA*EXP(-ALPHA*(IAGE+TIME))
> EN=(C01-(C01*C01-FZ1*(C01*C01-FZ))**0.5)/FZ1;EN=ENDOG. CP(0)
> CS=EN*(ALPHA-BETA)
> ;CSS=EN(T=-IAGE)
> CSS=CS/((K-BETA)*EXP(-ALPHA*IAGE)+(ALPHA-K)*EXP(-BETA*IAGE))
> IPR1=F+CSS/(ALPHA-BETA)*(EXP1+EXP2) ;PLASMA CONC.
> IPR2=A(2)/V1*K21/K12+CSS/(ALPHA-BETA)*(EXP3-EXP4);TISSUE CONC.
>
> RZ=CSS/CLE
> ;ENDOG. RATE
> IDIF=CP-IPR1
> W=(1+IPR1*IPR1*THETA(9)*THETA(9))**0.5
> Y=IPR1+W*THETA(10)*ERR(1)
> $THETA
> .
> .
> .
> $THETA
> $SIGMA 1
> FIXED
> ;VARIANCE FOR ERR(1)
> $EST NOABORT NUMERICAL SLOW METHOD=1 INTERACTION LAPLACIAN POSTHOC
> SIG=6 MAX=9999 PRINT=1 MSFO=VER1.MSF
> $COVARIANCE MATRIX=S SLOW COMPRESS PRINT=E
> $TABLE ID TIME ALPHA CLD CLE BETA V1 RZ NOPRINT FILE=VER1.TAB
> $TABLE ID TIME C01 ER=COM(1) EN CSS IPR1 IPR2 NOPRINT FILE=VER1.TAB
> $TABLE ID TIME IAGE K12 K21 K R1 IDIF NOPRINT FILE=VER1.TAB
> $SCAT CP VS IPR1 UNIT
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
[EMAIL PROTECTED] tel:+64(9)373-7599x86730 fax:+64(9)373-7090
www.health.auckland.ac.nz/pharmacology/staff/nholford