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Dear all,
I was wondering if someone has experience with feedback model. I am trying to code a model that drug
inhibits the production of response (turnover model 1) and the moderator stimulates the loss of
response.
deriv(R= Kin * (1 - Imax * C / (C + IC50)) - Kout * R* (1+ M)
deriv(M = Ktol*R -Ktol*M)
My questions are:
1) Initial estimates: can I use the same method as turnover model I to estimate the Kin, Kout, I
max, IC50?
Kout= -slope (initial deline phase)
Kin=Kout*R0
Imax= I-Rmax/R0
2) The sequence: is this correct sequence? ( same as model I?)
sequence{R =R0= Kin / Kout }
3) How to estimate Ktol?
4) In Gabrielsson and Weiner's PKPD book (Fourth edition, page 1003), it says the R0= -0.5+
SQRT(0.25+Kin/Kout)
Should the sequence use:
sequence{R =R0= 0.5+ SQRT(0.25+Kin/Kout)}
Many thanks in advance,
Bo
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