Hi Orlando,

This is somewhat dependent on how exactly you want the fraction to be coded.  
Most likely, you want to restrict the volume to be positive and not bounded 
between 0 and 1 (i.e. it is ≥0).  Given that, you can define V3 as:

V3=EXP(THETA(8))*V1

You would then just exponentiate THETA(8) to find the fraction.

You can separately estimate the volume using the same ETA as the parent central 
volume as:

V3=THETA(8)*EXP(ETA(1))

That way, it won’t explicitly be a fraction of the parent, and that may lead to 
a more stable model.

Thanks,

Bill

From: [email protected] [mailto:[email protected]] On 
Behalf Of Carlos Orlando Jacobo Cabral
Sent: Monday, May 21, 2012 2:19 PM
To: nonmem users
Subject: [NMusers] VD as a fraction of another VD

Dear NMusers,

Hi, I have data of a parent drug (intravenously administered) and its 
metabolite, ¿How can I code the volume of distribution of metabolite as a 
fraction of the central volume of parent?
An example of the model that I want to fit is:

$PK

V1=THETA(1)*EXP(ETA(1)) ; Central Volume of parent
V2=THETA(2)*EXP(ETA(2)) ; Peripheral Volume of parent
Q=THETA(3)          ; intercompartmental clearance

V3= ????????????  ; Volume of metabolite as a fraction of V1 with variability

CL1=THETA(5)*EXP(ETA(4)) ;  Formation clearance of metabolite
CL2=THETA(6)*EXP(ETA(5)) ; Elimination clearance of metabolite
CL0=THETA(7)*EXP(ETA(6)) ; Parent drug excretion by routes other than formation 
of metabolite



   - Thank you in advance.

Orlando.


PhD student Carlos Orlando Jacobo Cabral
Departamento de Farmacología, Lab.34
Centro de Investigación y de Estudios Avanzados del I. P. N.
Email: [email protected]<mailto:[email protected]>; 
[email protected]<mailto:[email protected]>
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