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Re: simultaneous PK/PD

From: Nick Holford <n.holford>
Date: Thu, 24 Jun 2010 08:28:03 +0200

Jeroen,

There is no need to defined a different EPS for PK and PD. Every
observation record has a new random instance of EPS associated with it.
So if there is only one random residual error parameter (PK or PD) then
only one EPS is needed.

In this particular case EPS(1) is always mean 0 and variance 1 but it is
scaled by THETA(8) for PK and THETA(9) for PD so that the residual error
is appropriate for the type of observation.

There is no implied correlation between the random residual error.

Nick

Elassaiss - Schaap, J. (Jeroen) wrote:
> Dear Hauke,
>
> Moreover in this case, I would assign a different sigma to PK and PD.
> Your model actually states the belief that the variability in PK and
> PD are 100% correlated (unless they are always measured at different
> times). If you have background support for such a model it is fine,
> but in general I would advice to associate EPS(1) with THETA(8) for PK
> and EPS(2) with THETA(9) for PD.
>
> Hope this helps,
> Jeroen
>
>
> Modeling & Simulation Expert
> Pharmacokinetics, Pharmacodynamics & Pharmacometrics (P3) - DMPK
> *MSD*
> PO Box 20 - AP1112
> 5340 BH Oss
> The Netherlands
> jeroen.elassaiss
> T: +31 (0)412 66 9320
> F: +31 (0)412 66 2506
> www.msd.com
>
>
> ------------------------------------------------------------------------
> *From:* owner-nmusers
> [mailto:owner-nmusers
> *Sent:* Wednesday, 23 June, 2010 14:54
> *To:* nmusers
> *Subject:* [NMusers] simultaneous PK/PD
>
> Dear NMusers,
>
>
>
> I want to combine my sequential PK and PD model to one simultaneous
> model. In both models I used an exponential error model
> (log-transformation). When I write the model as follows, NONMEM gives
> me this error message:
>
>
> 326 RANDOM VARIABLE IS DEFINED IN A NESTED IF STRUCTURE.
>
>
>
> Leaving out the condition C.GT.0 will also lead to errors. Is there
> another way to write this?
>
>
>
> Thanks
>
>
>
> Hauke
>
>
>
>
>
> $ERROR
>
> C1=(A(1)/V1)
>
> C3=A(3)
>
>
>
> IPRE=0
>
>
>
> IF (M1H2.EQ.1) THEN
>
> IF (C1.GT.0) IPRE = LOG(C1)
>
> IRES = DV-IPRE
>
> W = EPS(1)*THETA(8)
>
> Y = IPRE+W
>
> ENDIF
>
>
>
> IF (M1H2.EQ.2) THEN
>
> IF (C3.GT.0) IPRE = LOG(C3)
>
> IRES = DV-IPRE
>
> W = EPS(1)*THETA(9)
>
> Y = IPRE+W
>
> ENDIF
>
>
>
> DEL = 0
>
> IF(W.EQ.0) DEL = 1
>
> IWRE = IRES/(W+DEL)
>
>
>
> $SIGMA
>
> 1 FIX
>
>
>
> -----------------------------
>
> Hauke Rühs
>
> Apotheker
>
> Pharmazeutisches Institut
>
> - Klinische Pharmazie -
>
> An der Immenburg 4
>
> 53121 Bonn
>
>
>
> Tel: + 49-(0)228 73-5781
>
> Fax: + 49-(0)228 73-9757
>
>
>
> www.klinische-pharmazie.info <http://www.klinische-pharmazie.info/>
>
>
>
>
>
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--
Nick Holford, Professor Clinical Pharmacology
Dept Pharmacology & Clinical Pharmacology
University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand
tel:+64(9)923-6730 fax:+64(9)373-7090 mobile:+64(21)46 23 53
email: n.holford
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford


Received on Thu Jun 24 2010 - 02:28:03 EDT

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