I have a PK/PD modeling question using Phoenix PML. I wrote a user defined model to model tumor growth kinetics and inhibition by anti-tumor agent. The model works quite well when I modeled PK at 4 different dose levels simultaneously (using naïve pool Population function), and then freeze the PK with one set of PK parameters, followed by tumor kinetic model simultaneously at 4 dose levels. But I have another case in which the PK was non-linear, and the data was sparse, incorporating non-linear function did not work well. I modeled the 4 doses separately with 4 sets of different PK parameters (ka, V/F, ke), I know there is a way to specify these separate PK parameters for each dose level, and model the PD (tumor kinetics) simultaneously, so there is only one set of PD parameters. In the Phoenix code, how do I specify that and link and freeze different set of PK parameters to different dosepoint (Aa)? Your help is greatly appreciated. Thanks very much, Chun Li
Dear Chin I am attaching an example that I hope answer your question. The idea is to define these 4 PK sets as covariate and ask the program to use them. Please let me know if it is clear. The model is the last one. best Regards; Serge
The project is now attached
did not work. I am trying again [file name=chun_li_OFFICIAL.phxproj size=856563]Certara | Drug Development Solutions (836 KB)
Thanks Serge for the prompt reply. I could not open the project because I have an older version of Phoenix 6.2. Need our IT to upgrade to the newest version. Thanks, Chun
Dear Chin This is the code I generated. I attached the file too. Yes you need to upgrade your version. best Serge test(){ # comment: specify PK model, ie, 1-compartment oral PK model deriv(Aa = - Ka * Aa) deriv(A1 = Ka * Aa - Ke * A1) dosepoint(Aa) # define the 3 PK as covariate where theier values change with dose and show # up in the dataset covariate(kacov) covariate(kecov) covariate(vcov) covariate(dosing) Ka=kacov V=vcov Ke=kecov C = A1 / V # comment: specify and freeze PK parameters obtained from PK model # fixef(Ka(freeze) = c(, 0.560916, )) # fixef(V(freeze) = c(, 11654.7, )) # fixef(Ke(freeze) = c(, 0.354519, )) # comment: specify transit compartment, tumor kill kinetic model # comment: R0 is the starting tumor volume just before compound dosing R0 = 185 K=Kmax * C^n / ( KC50^n + C^n) deriv(E1 = (Kng - K) * E1) deriv(E2 = KE1 - ktranE2) deriv(E3 = ktranE2 - ktranE3) deriv(E4 = ktranE3 - ktranE4) E = E1 + E2 + E3 + E4 sequence{E1 = R0} sequence{E2=0} sequence{E3=0} sequence{E4=0} error(EEps = 1) observe(EObs = E + EEps) # comment: specify initial estimates for tumor kinetic model fixef(Kng = c(, 0.006, )) fixef(ktran = c(, 0.002, )) fixef(Kmax = c(, 0.05, )) fixef(KC50 = c(, 800, )) fixef(n = c(, 1, )) } [file name=DATA_FOR_FIT.xls size=31232]Certara | Drug Development Solutions (30.5 KB)