Anyone tried modelling turnover model using the response data which is difference of drug treated and vehicle treated animals. Baseline in this case is zero. There is case study PD28 in Johan Gabrielsson/Dan Weiner book ‘PK&PD data analysis: concepts and applications’ which is similar to this. That case study describes Winnonlin code in it. Can anyone think of PML code equivalent of that code please? It appears that we need to have initial condition that need to be set by sequence statement and following is my try but now working:
deriv(E = Kin * (1 - Imax * C / (C + IC50)) - Kout * E-E0)
sequence{E=E0}
E0 = Kin / Kout
Kin=1
Many thanks Dr Weiner, I am able to fit the data now and it has worked well.
It appears that once we change the observe statement, then for some reason, ‘E vs t’ or any of ‘E’ visualisation disappears from the ‘initial estimates’ window.
This was not issue because I determined initial estimates based on theory described in your book and this is also explained in previous PML webinars of turnover model.
Thanks again, much apprecaited.
My apologies for coming back. I was thinking lately the need to fix Kin=1. Is it needed to fix Kin to fix to constant value (1) or is it parameter estimated along with Kout, Imax and IC50. Also I am keeping bounds for Imax as, minimum value 0 to maximum value=1.
Any thoughts in this direction will be highly appreciated.