Calculating average occupancy and fix at 50% at time point 24h

Phoenix Certara Forums Modelling and Simulation
1

Hi.

Based on the following Phoenix WNL code (see below) I want to calculate the average occupancy (Occ_avg) over time, and then tell Phoenix to fix the Occ_avg to 50% at time point 24 h in order to estimate the IC50 value. Please, is there anyone who know how to code this in Phoenix WNL?

Many thanks.

//Therese Ericsson

My Phoenix code:

###Compound PK
deriv(A1 = - Cl * C - Cl2 * (C - C2))
deriv(A2 = Cl2 * (C - C2))

dosepoint(A1)
C = A1 / V
C2 = A2 / V2

stparm(V = tvV)
stparm(V2 = tvV2)
stparm(Cl = tvCl)
stparm(Cl2 = tvCl2)

fixef(tvV = c(, 0.035, ))
fixef(tvV2 = c(, 0.04, ))
fixef(tvCl = c(, 0.09, ))
fixef(tvCl2 = c(, 0.02, ))

error(CEps = 1)
observe(CObs = C * (1 + CEps))

###Inhibition and occupancy (%)
#Receptor binding potential at baseline = BP0
#Imax = maximum inhibitory effect of drug on BP
#IC50 = plasma concentration associated with a 50% decrease of BP

#Change in binding potential caused by the drug/compound
BP = BP0 * (1-((Imax * C)/(IC50 + C)))

#Occ = ((BP0 - BP)/BP0) * 100
Occ = (((Imax * C)/(IC50 + C)) / BP0) * 100

stparm(BP0 = tvBP0)
stparm(Imax = tvImax)
stparm(IC50 = tvIC50)

fixef(tvBP0(freeze) = c(,1,))
fixef(tvImax(freeze) = c(,1,))

fixef(tvIC50 = c(, 0.000175, ))

2

Hi Therese, I;m not sure I understand your question, I can see you’ve got the syntax for freezing a parameter in your code already. However I don’t really get what you are trying to do with

‘fix the Occ_avg to 50% at time point 24 h in order to estimate the IC50 value.’

maybe if you could post a project containing an example of your data, (or just a worksheet of a single profile) someone could understand better what you’re trying to achieve?

Simonm

3

Hi Simon.

Thanks for your reply.

I have solved the issue simply by including the following text in my model code:

deriv(Occ_avg= Occ/24) #Dose interval 24h
error(Occ_avgEps = 1)
observe(Occ_avgObs = Occ_avg * (1 + Occ_avgEps))

In my data file I have then included a column called “average occupancy”, and defined an observed average occupancy at time point 24h as 50%. However, this means that I estimate the average occupancy, not really fix it to 50%.

Regards,
Therese