I am wondering how I start to build TMDD (target-mediated drug disposition) model for mAb with new PHX Model Language. I would prefer to use a built-in model. Thanks.
TMDD models can be built in Phoenix by selecting any built-in model and clicking “Edit as Textual”. In the Model section in the Setup Tab, enter the following code: test(){ DOSE = 2.7 #IV bolus dose, in the same unit as the numerator of the concentration unit deriv(CMAB = -CMABKelmAb - KonCMAB*(CAg - CComplex) + KoffCComplex) #differential equation for the concentration of molecular antibody error(CMABEps=1) #initial estimate for the standard deviation of the residual error observe(CMABObs = CMAB+CMABEps) #observe statement dictates what variables will need to be mapped (CMABObs) in the mappings panel and also sets the structure of the error model (additive). deriv(CComplex = Kon(CAg - CComplex)CMAB - (Koff + KelAbAg)CComplex) #differential equation for the concentration of antigen/antibody complex deriv(CAg = Ksyn - KelAbAgCComplex - KelAg(CAg - CComplex)) #differential equation for the concentration of antigen Ksyn = KelAg*CAg0 PctRO = (1-((CAg - CComplex)/CAg0))*100 #Percent receptor occupancy sequence{ #Initial conditions at time 0 CComplex = 0; CMAB = DOSE/Vc; CAg = CAg0; } stparm(Vc = tvVc) #structural parameters stparm(KelmAb = tvKelmAb) stparm(KelAbAg = tvKelAbAg) stparm(Kon = tvKon) stparm(Koff = tvKoff) stparm(KelAg = tvKelAg) stparm(CAg0 = tvCAg0) fixef(tvVc = c(, 0.2, )) #fixed effects and intial estimates fixef(tvKelmAb = c(, 0.044, )) fixef(tvKelAbAg = c(, 0.21, )) fixef(tvKon = c(, 1, )) fixef(tvKoff = c(, 1, )) fixef(tvKelAg = c(, 0.7, )) fixef(tvCAg0 = c(, 55, )) } Currently, there is no built in TMDD model, but I will enter an enhancement request to add one to a future release. Best regards, Emily Colby