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Question about interoccation variability

From: Xu, Claire <smartxucong>
Date: Tue, 10 Jul 2012 16:46:19 -0400

Hi, everyone:
I am trying to develop a pop PK model for a compound with a large
variability in absorption. I have difficulty in fitting the absorption
phase, especially the Cmax. Some of the subjects are underpredicted while
some subjects are overpredicted.
Since the study is a four-way cross-over study with 5 different occasions,
I am thinking about incorporating interoccasion variability (IOV) on Ka in
my model. I tried to test IOV using the code:
IF OCC==1 BOVKA=ETA(1)
...
IF OCC==5 BOVKA=ETA(5)
KA=THETA(1)*EXP(BOVKA)
$OMEGA BLOCK (1); for OCC=1
0.16
$OMEGA BLOCK(1) SAME; for OCC=2
...
 $OMEGA BLOCK(1) SAME; for OCC=5

But it didn't improve the fitting. Then I tried to remove the "SAME" and
five different estimation of ETAs were obtained. The fitting wasn't really
improved. Can anyone comment on that whether it is oaky to have 5 different
ETAs on one parameter in the model according to different occasions?
Also, is there any suggestion to improve the fitting of absorption? I also
tried ALAG model but not improve the fitting either. The Ka is kind of
large for my compound (around 1.5). some of the subjects have the first
sample as Cmax but not in other subjects. some of the subjects showed a
second peak during distribution in some occasions but not in other
occasions. Not sure how to handle all these visibilities in my data and get
the good fit of absorption phase.
Any suggestions would be appreciated.
Thanks!
Best,
--
Xu, Claire
Ph.D Candidate
Division of Clinical Pharmacology, Wishard Hospital
Indiana University School of Medicine
1001 West 10th Street, Myers W7122
Indianapolis, IN 46202
T - 317/7558242

Received on Tue Jul 10 2012 - 16:46:19 EDT

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