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RE: simultaneous PK/PD

From: Elassaiss - Schaap, J. - <jeroen.elassaiss>
Date: Thu, 24 Jun 2010 07:25:08 +0200

Dear Hauke,
 
Nonmem cannot handle random variables defined in nested conditions. See =
the help entry on abbreviated code:
"Random variables cannot be defined within nested conditionals, i.e.,
within a conditional structure beginning with an IF and containing
another IF. The use of ELSEIF ... THEN implies a nested conditional."
The usual way of handling this is to define a dummy variable to set the =
condition, but you do not even need this in your case as Brendan and =
Katya pointed out.
 
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.
 
You may even skip zero testing by request (ONLYOBS) after $ERROR if you =
always have positive predictions of C1 and C3 during observation records =
(e.g., a PK model without lagtime), see nmhelp on $ERROR.
 
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
On Behalf Of Hauke Rhs
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 Rhs

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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Received on Thu Jun 24 2010 - 01:25:08 EDT

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