- On 7 Jan 2014 at 21:38:34, Bo Liu (bliu.at.GNF.ORG) sent the message

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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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