Re: Steady state dose
Joanna,
I don't know of any way to request a positive SS solution. However I wonder if the problem is related to the way you use the SS data item in the code.
HIV = SS*THETA(9)*EXP(ETA(9))
Usually there is just one record with SS=1 at the start of each subject's records. If this is the case then the value of HIV will be zero at all times after the SS=1 record. Does this make sense for your model?
I am not even sure that SS would have the value of 1 during the calculation of the steady state solution -- although that would be a reasonable assumption that could be confirmed by someone such as Alison Boeckmann.
Nick
PS NONMEM calculates steady state amounts in compartments -- it does not calculate steady state doses.
Quoted reply history
On 15/10/2011 3:07 a.m., Joanna Lewis wrote:
> Dear NONMEM users,
>
> I have a question about NONMEM's calculation of steady-state doses.
>
> I am trying to model a system with two compartments. I want my t=0 boundary condition to be that the system is at steady-state, with a rate of cell death/clearance from one of the compartments which is higher than for all t>0. Unfortunately, I don't think there is an analytic solution for this steady state (see code copied below).
>
> From an old NMusers thread ( http://www.mail-archive.com/ [email protected] /msg00584.html ), I found out that NONMEM will find the steady state if you give it SS=1, RATE=0, AMT=0 in a t=0 record in the data file. When I tried this though, NONMEM found the wrong root of the steady-state equation (a negative one). Do you know if there is a way of making sure the steady state it finds is the positive one? For the moment, I have been initialising the compartments near to the steady state and at t=-(a lot), and letting them equilibrate, but I think this is slowing down my runs and would prefer to use another method.
>
> Thank you very much in advance for any advice you can offer.
> Joanna Lewis
>
> PhD student
> UCL Institute for Child Health
> 30 Guilford Street, London WC1N 1EH
>
> $PROBLEM hapuarachchi0_15sep_1
> $INPUT ID BAGE AGE WEEK TIME CD DV AMT RATE SS TYPE CMT IG
> $DATA data.csv IGNORE=@
>
> $SUBROUTINE ADVAN6 TOL=5
>
> $MODEL
> COMP=(X)
> COMP=(Y)
>
> $PK
> ANO = THETA(1)*EXP(ETA(1))
> EP = THETA(2)*EXP(ETA(2))
> DEO = THETA(3)*EXP(ETA(3))
> SIG = THETA(4)*EXP(ETA(4))
> SCA = THETA(5)*EXP(ETA(5))
> Q = THETA(6)*EXP(ETA(6))
>
> THE = THETA(7)*EXP(ETA(7))
> RHO = THETA(8)*EXP(ETA(8))
>
> HIV = SS*THETA(9)*EXP(ETA(9))
>
> $DES
>
> ALP = ANO*EXP(-EP*SCA*A(1))
> DEL = DEO*EXP(SIG*SCA*A(1))
> MU = Q*A(2) + HIV
>
> DADT(1) = THE + 2*RHO*A(2) - ALP*A(1) - DEL*A(1)
> DADT(2) = ALP*A(1) - RHO*A(2) - MU*A(2)
>
> $ERROR
> IPCD = A(1)+A(2)
>
> Y = IPCD + IPCD*EPS(1)
>
> $THETA
>
> ...etc..
>
> $OMEGA
>
> ...etc...
>
> $SIGMA
>
> ...etc...
>
> $ESTIMATION MAXEVAL=0 METHOD=1 INTER SIGDIG=1 PRINT=1
>
> $TABLE
>
> ...etc...
--
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: [email protected]
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford