Hi, I have built the parent drug POPPK model and now I want to add the metabolite model-but- I have no idea how to add it. Is it like in nonmem?Do I need to calculate the values for V/Km/Vmax (I have M-Menten) and add them into separate columns in the data sheet?How do I fix the parent drug model and how do I write the metabolite model? Any ideas would be helpful! Thanks, Georgia
Hi Georgia, In Phoenix every entity that is modeled should have a different column. To add a new observation you can go from gui to graphical mode “draw” the additional compartments then you need also to add the green boxes (observations) adjust the names. Make sure to have your mapping right. If you don’t want to fit all the model simultaneously fixing the parameters of parent can be done by merging the individual parameters and using them as covariates. Please let me know if you have any question. If you give more detail on your data/model we can help you more. Samer
Hi Samer, Thanks for your answer. The parent model is 1cp with Michaelis Menten elimination, non-diagonal and weight as a cov to the volume. I want to add the metabolite (still doing some research for the elimination) and get the estimates for the metabolite but I want to fix the parameters for the parent drug. I n nonmem you have to add in different columns for each patient the calculated parameters (V, Km, Vmax), so that the model uses them for each patient (fixed) and then you get the estimates for the metabolite. In Phoenix I have to use the population estimates (theta), fix them as covariates and then run the metabolite model?Did I get it correctly? Thanks again for the help. Georgia
Hi Georgia, Similar to NONMEM, in phoenix as well you need to add in different columns for each patient the calculated parameters (V, Km, Vmax), Then you tell the model to use corresponding column for each parameter. I am attaching one of my model codes to give you an idea: # note that I simplified my model to make it simpler # I did not run it but ti will give the general principle # I supposes that you merged your data with the individual parameters # you define stparm(V = VI) # where VI is a column in your data # test(){ deriv(A1 = - (Cl * C) + (Aa * Ka)- (Clform * C)) deriv(Aa = - (Aa * Ka)) deriv(A1met = - (CLmet * C1met) + (Clform * C)) C = A1 / V dosepoint(Aa, idosevar = AaDose, infdosevar = AaInfDose, infratevar = AaInfRate) C1met = A1met / Vmet error(CEps = 2.21884) observe(CObsmet = C1met + CEps * (1 + C1met * CMixRatio)) stparm(V = VI) stparm(Cl = (1-fm)*ClI) stparm(Ka = KaI) stparm(Vmet = tvVmet (BW/70)^dVdBW * exp(nVmet)) stparm(CLmet = tvCLmet (BW/70)^dCldBW exp(nCLmet)) stparm(Clform = fmClI) covariate(BW) covariate(ClI) covariate(VI,KaI) fixef(tvVmet = c(0, 656, )) fixef(tvCLmet = c(0, 138, )) fixef(fm = c(0, 0.6, 1)) fixef(CMixRatio = c(0, 0.102878, )) fixef(dVdBW(enable=1)(freeze) = c(0, 1, )) fixef(dCldBW(enable=4)(freeze) = c(0, 0.75, )) ranef(diag(nVmet, nCLmet) = c(1, 1)) }
Thanks for the answer. I will try to adjust the example model to my model and I hope it runs successfully! Georgia
Hi, is it possible to post the graphical version of the model? Thanks, Georgia
Georgia, there was a similar conversation already on the forum here;Certara | Drug Development Solutions the lisa2.phxproj there has the model in graphical mode. Simon 
Thanks for the graph. Also, Iwould like to ask one more thing. The metabolism of cyclophosphamide (the drug I am studying) into 4-OH-CYexhibits autoinduction. So, I am trying to incorporate into the metabolite model a Kenz constant, but I don’t know how to do it. Any ideas? Thanks so much for all the help. Georgia