From:
Subject: [NMusers] Mixture models in NONMEM
Date:Thu, 17 Apr 2003 16:09:18 -0400

Dear all:
 
I am trying out some mixture models in NONMEM, however, the models appear to be
somewhat too sensitive to initial estimates.  
 
Specifically, this is a two compartment oral model with mixture on
CL and V2, using the MIX=MIX function with the Advan4, Trans4 subroutine.
 
Can someone pls. shed some light on the utility of the mixture models and
the apparent sensitivity to initial estimates?  Any feedback is much appreciated.
 
Best regards, 
Rajesh 

Rajesh Krishna, PhD, FCP 
US Clinical Pharmacokinetics 
Aventis Pharmaceuticals, Inc. 
Mailstop: BWM-303A 
1041 Route 202-206 
P. O. Box 6800 
Bridgewater, NJ 08807-0800
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From: "Bhattaram, Atul" 
Subject:RE: [NMusers] Mixture models in NONMEM
Date:Thu, 17 Apr 2003 16:32:13 -0400

Hello Rajesh
 
It would be interesting to know why you selected MIXTURE model. Was it based on some prior
information (phenotype) or some assumption testing. I remember a reference in which they used
MIXTURE model because they had polymorphism in metabolism. Use of mixture model might help
in identifying why you have two proportions which must be reflected as bimodality etc in your plots.
 

Venkatesh Atul Bhattaram 
CDER, FDA.
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From:"Sam Liao" 
Subject: RE: [NMusers] Mixture models in NONMEM
Date: Thu, 17 Apr 2003 19:14:20 -0400

Hi Rajesh:
 
The problem may not be the mixture model.  The two-compartment oral model itself is very sensitive
to the initial estimates.  You need to find ways to get good initial estimates.   Also try to model F1 with
the mixture model because the first-pass metabolism may be affected by genotype.  We may be able to
help you further if you can share your control file.
 

Best regards,

Sam Liao, Ph.D.
PharMax Research
20 Second Street,
PO Box 1809,
Jersey City, NJ 07302
phone: 201-7983202
efax: 1-720-2946783
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