PK/PD problem using ADVAN6
From: Kakkar, Tarundeep [mailto:tarundeep.kakkar@spcorp.com]
Subject: PK/PD problem using ADVAN6
Date: Friday, March 01, 2002 8:09 AM
Hi,
I sent a question to nmusers. Someone suggested that the model needs ERR(1)
rather than ETA(1) for the $OMEGA for the single subject and I should go
with population modeling straightaway. I went and did that, but I'm not
getting satisfactory results, the model converges but the fit isn't correct.
The PD measurements should start coming back at later time-points according
to the observed data, but in the fit the PD keeps on going down.
So, I'm forwarding the email I sent to the nmusers group. Is there
something wrong the way I coded the data file? Does it need a fictitious
compartment (CMT = 2). Does having AMT =1 at the 0 hr value for CMT=3
somehow messes it up?
I hope you can help me.
Tarun
I am trying to fit an Indirect response model to a
drug given orally once a week. There are no PK
measurements. I have a baseline value for each
subject and PD measurements every week for 28 days (0,
7, 14, 21 and 28 days). I'm trying to troubleshoot
this with one subject before I go to fitting all
subjects and am having problems with the model
converging.
I don't know if the data file is setup incorrectly or
if the model is incorrect or both. Is it
overparameterized (4 estimates and only 5 observed
values)? If it's overparametrized, how do I force it
to not estimate ETA(1)?
I was able to get a decent fit for this in WinNonlin.
I would really appreciate if someone could help me
with this.
Thanks
Tarun
The model I wrote goes something like this (Time in
hours):
$PROB POP PK/PD Model $DES
$INPUT ID VOL TIME DV AMT CMT
$DATA data.csv IGNORE=C
$SUBROUTINE ADVAN6 TRANS=1 TOL=3
$MODEL NCOMP=3
COMP=(GUT)
COMP=(CENTRAL)
COMP=(EFFECT)
$PK
KA=0.042
KE=0.022
V2=VOL
S2=V2
IC50=THETA(1);*EXP(ETA(1))
KOUT=THETA(2);*EXP(ETA(3))
KIN=THETA(3);*EXP(ETA(2))
F3=KIN/KOUT
$DES
DADT(1)=-KA*A(1)
DADT(2)=KA*A(1)-KE*A(2)
CE=A(2)/V2
DRUG1=1-CE/(CE+IC50)
DADT(3)=KIN*DRUG1-KOUT*A(3)
$ERROR
Y=F+ETA(1)
IPRED=F
and so on ....
Data file:
CID VOL TIME DV AMT CMT
1 91.825 0 . 3000000 1
1 91.825 0 . 1 3
1 91.825 0 43916 . 3
1 91.825 168 . 3000000 1
1 91.825 168 16638 . 3
1 91.825 336 . 3000000 1
1 91.825 336 3349 . 3
1 91.825 504 . 3000000 1
1 91.825 504 6183 . 3
1 91.825 672 . 3000000 1
1 91.825 672 5707 . 3
***************************************************************
This message and any attachments is solely for the intended recipient. If
you are not the intended recipient, disclosure, copying, use, or
distribution of the information included in this message is prohibited --
please immediately and permanently delete this message.