Re: ADVAN3 TRANS3 Problem
Date: Wed, 03 Nov 1999 15:53:49 -0800
From: LSheiner <lewis@c255.ucsf.edu>
Subject: Re: ADVAN3 TRANS3 Problem
You must write your PK code so that the model is a feasible model. That means, among other things, VSS>V. A simple way to accomplish this is to parameterize as follows:
> $PK
> CL=THETA(1)
> V=THETA(2)
> VSS= V + THETA(3)
> Q=THETA(4)
>
> K=CL/V
> K12=Q/V
> K21=Q/(VSS-V)
>
> $THETA
> (0,4)
> (0,7)
> (0,3)
> (0,4)
Note:
1. THETA(3) is constrained >0 so VSS is always >V
2. THETA(4) is not the typical value of VSS; the typical value of VSS is THETA(3)+THETA(4)
3. When you add etas and use FO (METHOD=0) above will still work, but if you want to use FOCE (or other METHOD=1) you will have to assure that the individual values of VSS (i.e., when ETAs are nonzero) are > V, which can be tricky.
4. I removed all upper bounds on parameters (in $THETA). These are almost NEVER indicated. Bounds should be used ONLY to constrain a model to a feasible region, as for example the use of lower bounds of zero on physical quantities that cannot physically be negative.
LBS.
Lewis B Sheiner, MD Professor: Lab. Med., Biopharm. Sci., Med.
Box 0626 voice: 415 476 1965
UCSF, SF, CA fax: 415 476 2796
94143-0626 email: lewis@c255.ucsf.edu