NONMEM Users Network Archive

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Re: Code to avoid flip-flop kinetics

From: Paolo Denti <paolo.denti>
Date: Fri, 07 Aug 2009 21:43:46 +0200

Thanks Samer,
I have seen that option too and tried it, but unfortunately it does not
seem to have any effect... Any clues about this?

The trick with the initial estimates is what I am currently using, but
it is a bit frustrating, especially if you aim at obtaining a run with a
successful covariance step...

Thank you!
Paolo


Samer Mouksassi wrote:
> From NONMEM help it seems that there is a NOABORTFIRST option but I never used it:
>
> $THETA value1 [value2] [value3] ...
> [NUMBERPOINTS=n]
> [ABORT|NOABORT|NOABORTFIRST]
>
>
>
> Otherwise you can change your initial estimates appropriately so the
> first iteration starts!
>
>
>
> Samer
>
>
>
>
>
>
>
> Samer Mouksassi Pharm.D.
>
> Senior Associate Scientist
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> ------------------------------------------------------------------------
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> *From:* owner-nmusers
> [mailto:owner-nmusers
> *Sent:* Friday, August 07, 2009 11:19 AM
> *To:* nmusers
> *Subject:* [NMusers] Code to avoid flip-flop kinetics
>
>
>
> Dear NMUsers,
> having to deal with the flip-flop kinetics phenomenon, I had a look at
> previous posts on the NMusers list.
> I found this post particularly enlightening:
> http://www.cognigencorp.com/nonmem/nm/99aug072003.html
>
> Some code was proposed to avoid the flip-flop at population and
> individual level. Here's a not-so-brief summary.
>
> This parameterization solves the issue at population level:
> CL=THETA(1)*EXP(ETA(1))
> V=THETA(2)*EXP(ETA(2))
> TVKE=THETA(1)/THETA(2)
> TVKA=TVKE+THETA(3)
> KA=TVKA*EXP(ETA(3))
>
> However, it does not prevent the phenomenon occurring at individual
> level. Vlamidir Piotrovsky proposed the code below, which does solve
> the problem at individual level, but makes the interpretation of the
> results a bit awkward and introduces correlation among the model
> parameters. In particular, variance of ETA3 was greatly increased.
> CL=THETA(1)*EXP(ETA(1))
> V=THETA(2)*EXP(ETA(2))
> KE=CL/V
> KA=KE+THETA(3)*EXP(ETA(3))
>
> Another approach, suggested by Nick Holford, implements error recovery
> using EXIT 1. The code is reported below:
> CL=THETA(cl)*EXP(ETA(cl))
> V=THETA(v)*EXP(ETA(v))
> KA=THETA(ka)*EXP(ETA(ka))
> K=CL/V
> IF (KA.LE.K) EXIT 1 101 ; try again (PREDERR message error code 101)
>
> As far as I understand, this interrupts the computation whenever the
> flip-flop occurs and lets NONMEM restart. However, if such an error
> arises at initialization, NONMEM does not recover and the run goes no
> further. Nick probably experienced something similar, but apparently
> received no answer
> http://www.cognigencorp.com/nonmem/nm/99oct072004.html
>
> Does anyone know of a way around this drawback? Or have other code to
> deal with flip-flop kinetics?
>
> Thank you in advance,
> Paolo
>
>
>
> --
> ------------------------------------------------
> Paolo Denti, Post-Doctoral Fellow
> Division of Clinical Pharmacology
> Department of Medicine
> University of Cape Town
>
> K45 Old Main Building
> Groote Schuur Hospital
> Observatory, Cape Town
> 7925 South Africa
> phone: +27 21 404 7719
> fax: +27 21 448 1989
> email: paolo.denti
> ------------------------------------------------

--
------------------------------------------------
Paolo Denti, Post-Doctoral Fellow
Division of Clinical Pharmacology
Department of Medicine
University of Cape Town

K45 Old Main Building
Groote Schuur Hospital
Observatory, Cape Town
7925 South Africa
phone: +27 21 404 7719
fax: +27 21 448 1989
email: paolo.denti
------------------------------------------------


Received on Fri Aug 07 2009 - 15:43:46 EDT

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