From: PING CHEN chen.1016@osu.edu
Subject: [NMusers] Help on rounding error ( error=134) !
Date: Sun, 12 Nov 2006 17:24:52 -0500

Hi,

  I was trying to do the popPK for a unstable drug which will be converted into its
  metabolite quickly. We only measure the parent compound concentration which was far
  below the dose. For example, 120 umol was given as i.v infusion for 1 h but  the
  plasma concentration of the parent compound is only around 0.02-1.5 uM. I just tried
  the simple ADVAN3  TRANS4 as follows, however, the result turns out to be a very
  large V2 and very small CL and keeping giving the rounding error ( error=134)! Does
  anyone can help me figure it out?
  
$PK
   V1=THETA(1)*EXP(ETA(1))
   V2=THETA(2)*EXP(ETA(2)) 
   CL=THETA(3)*EXP(ETA(3))
   Q=THETA(4)*EXP(ETA(4))

   K=CL/V1
   K12=Q/V1
   K21=Q/V2
 
   S1=V1

$ERROR
   IPRED=F
   W=F
   IRES=DV-IPRED
   IWRES=IRES/W
   Y= IPRED+W*EPS(1)

$OMEGA 0.25
$OMEGA 0.5
$OMEGA 0.5
$OMEGA 0.5

$SIGMA 0.25

   Thanks a lot.

Ping
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From: Nick Holford n.holford@auckland.ac.nz
Subject: Re: [NMusers] Help on rounding error ( error=134) !
Date: Mon, 13 Nov 2006 11:50:39 +1300

Ping,

Did you look at the model predictions? If the predictions look Ok then you can ignore the
rounding error message. A visual predictive check would be a good way to decide if your
model predictions are OK.

You say CL is small and V2 is large. On what basis of prior knowledge do you judge them to
be small and large? Unless you have some good reason e.g. CL much bigger than cardiac output
then it isn't usually helpful to judge the numerical values to be small or large.

Nick
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New Zealand
email:n.holford@auckland.ac.nz tel:+64(9)373-7599x86730 fax:373-7556
http://www.health.auckland.ac.nz/pharmacology/staff/nholford/
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From: "Toufigh Gordi" tgordi@Depomedinc.com
Subject: Re: [NMusers] Help on rounding error ( error=134) !
Date: Sun, 12 Nov 2006 20:19:14 -0800

Hi Ping,

I am guessing that you have looked at some graphs of your data and can clearly see a bi-phasic
decline, or have some prior knowledge about the drug, and that's why you apply a 2-comp model. I
would suggest that early on in the model-building, you start with one ETA (my suggestion would
be CL or VC). If you find a model that does a relatively good job, you can start adding ETAs to
see whether they improve the fit.

I don't knwo about the NONMEM codes for various errors have have obviously not seen your data
but your problem might be due to over-parametrization.

Toufigh
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