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RE: Predict AUC based on trough concentrations

From: Hang, Yaming <yaming_hang>
Date: Thu, 18 Feb 2010 10:22:22 -0500

Dear All,

I'm grateful for the many responses that you posted to my question
regarding AUC prediction based on a few trough concentrations.

My final conclusion on this problem is that it is related to the
improper configuration of the SIZES file. Before this large scale
exercise, I did some thing similar with a much small trial (12 subjects
with less than 30 time points each) on my laptop, no problem with that
one at all. The initial error message with the large scale problem (run
on laptop) is about the MAXID parameter in SIZES file. Although I've
increased the value of MAXID and NO parameters and recompiled, there was
still error message. I was told by a colleague that if several other
parameters are not changed accordingly, the issue is not completely
solved. So eventually I run the NONMEM control file on Unix system where
much larger MAXID and NO are allowed, and it worked.

Thanks for your suggestions of adding an AUC compartment, this is
certainly something new I learned.

Kind regards,
Yaming



-----Original Message-----
From: Johan Wallin [mailto:WALLIN_JOHAN
Sent: Thursday, February 18, 2010 9:23 AM
To: Hang, Yaming
Subject: Re: [NMusers] Predict AUC based on trough concentrations

Yaming,
Maybe I misunderstood what you were trying to do here. As I interpret
you
were not simulating and reestimating, but rather just want to calculate
AUC:s based on the EBE parameters from sparse sampling? An easier way
would
be to simply calculate AUC in your original run, i.e. tabulating AUCi
based
on the CLi. That would eliminate the need for this second run, and
resetting the sizes.

/Johan
 

 Johan WALLIN PhD

 Research Scientist PK/PD/TS

 



 

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 Tel: +44 1276 483273 Fax: +44

 1276 484367

 www.lilly.co.uk

 



 

 

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             "Hang, Yaming"

             <yaming_hang

             k.com>
To
             Sent by: <nmusers

             owner-nmusers
cc
             bomaxnm.com

 
Subject
                                       [NMusers] Predict AUC based on

             17/02/2010 18:22 trough concentrations

 

 

 

 

 

 





Dear NONMEM Users,


I have a study where I'd like to predict AUC based on 2~3 trough
concentrations. There are about 500 subjects and I intend to predict
drug
concentration for 560 time points for each subject (10 time points/day *
56
days). The EBE for model parameters for each individual have been
generated and they will be fed into NONMEM for calculation of drug
concentrations. The following is the relevant NONMEM code:


$INPUT ID DOSE=DROP DAYN TIME AMT DV EVID MDV ADDL II CONC CLI V2I Q3I
V3I
Q4I V4I KAI F1I ALGI


$SUBROUTINES ADVAN12 TRANS4
$PK
  CL=CLI
  V2=V2I
  KA=KAI
  F1=F1I
  Q3=Q3I
  V3=V3I
  Q4=Q4I
  V4=V4I
  ALAG1=ALGI
  S2=V2I*624.709/1E6


$ERROR
   IPRED=F
   Y=F


$SIMULATION (26730517) ONLYSIMULATION SUBPROBLEMS=1


But I get error message like
0WARNING: MAXIMUM NUMBER OF THETA'S PLUS VARIANCE COMPONENTS
 EXCEEDS MAXIMUM NUMBER OF PARAMETERS THAT CAN BE ESTIMATED.
 SEE INSTALLATION GUIDE


I've increased LTH to 60 in file SIZES, LVR has a value of 30, but still
encounter this error message.


Does anybody have done similar thing in the past? What's likely to be
the
true issue here? Your suggestion will be greatly appreciated.


Yaming


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Received on Thu Feb 18 2010 - 10:22:22 EST

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