From: chang tien hung [mailto:tagsokim@ms95.url.com.tw]
Subject: [NMusers] a question about control file
Date: Wednesday, May 25, 2005 12:16 AM
dear all:
i have a program about carbamazepine
As follow is my control file
i find it difficult to find initial value which can run successful
all the result tell me " ETA=0 balabala...."
how can i make it better ?
thank you .
chang tien hung
;Model Desc: cbz control48
;Project Name: carbamazepine
;Project ID: MODEL 49
$PROB RUN# cbzcontrol69tets70
$INPUT C ID SEX AGE WT EVID TIME AMT SS II DV MDV VAL PHE PHB MD
$DATA datacbz1.csv IGNORE=C
$SUBR ADVAN2 TRANS2
$PK
TVCL1=THETA(1)*AMT**THETA(4)*WT**THETA(5)*AGE**THETA(6)
TVCL2=THETA(7)**VAL*THETA(8)**PHE*THETA(9)**PHB*THETA(10)**SEX
TVCL=TVCL1*TVCL2
TVV=THETA(2)
TVKA=THETA(3)
CL=TVCL*EXP(ETA(1)); Clearance (mL/kg/d)
V=TVV*EXP(ETA(2)); Central volume (mL/kg)
KA=TVKA; Absorption rate (/d)
S2=V; Scale factor
$ERROR
Y=F*EXP(ERR(1))
a question about control file
From: "Jakob Ribbing" Jakob.Ribbing@farmbio.uu.se
Subject: RE: [NMusers] a question about control file
Date: Wed, May 25, 2005 11:25 am
Dear Chang,
A good guess at initial estimates is easier to make if the parameters
that you estimate actually mean something. The current interpretation
of TVCL or THETA(1) is the typical value of clearance for an individual
which has been given a dose of 1 mg, weights 1 (kg?), is 1-year old of
SEX=0 (and on no concomitant medication). It is very hard to tell what
clearance this rather untypical individual might have. Center your
covariates on the median to get rid of this problem. Be sure you understand
which units your parameters have in order to get sensible initial estimates...
Further, you might consider using a more mechanistic model for the covariate
effects and enzyme induction. Using AMT to drive the induction (?) is probably
not what you want to do since this variable is set to zero at the time-points
where you have an observation in your data file. The induction on the other
hand has a time delay.
Good Luck! /Jakob
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