$ERROR block TMDD

Hello NONMEM Users, I’m relatively new NONMEM user. I have a drug which has showed TMDD (QSS) elimination in a previous study. In that study the drug binds to its target in central compartment. I only have the time course of the drug concentration. I tried to test the same model as well as Michaelis-Menten(MM)approach in my study but I failed. Reading some papers (Wan-Su Park et al, 2017Doi: 10.1111/bcpt.12675; P Dua et al, 2015 doi:10.1002/psp4.41 ), I found that the drug can only binds to its target in peripheral compartment or in both compartments at the same time. I want to try these models but I have trouble writing the $ERROR block. The code I have written for the model in which the drug binds to its target in peripheral compartment is given as following: $INPUT ID TIME AMT TINF RATE DV TAD MDV EVID $DATA ADPKD_100918.csv $SUBROUTINE ADVAN13 TOL=9 $MODEL COMP=(CENTRAL) COMP=(PERIPH1) COMP(PERIPH2) $PK TVCL=THETA (1) ;Linear elimination constant from the central Comp TVV1=THETA(2) ; Volume of Central Comp TVQ = THETA(3) ; Distributional clearance TVV2 = THETA(4) ; tissue distribution volumes TVKM= THETA (5) ; MM constant TVVM= THETA(6) ; Vmax TVKINT = THETA (7) ; Internalization constant TVKSYN = THETA(8) ; Synthesis rate constant TVKDEG = THETA(9) ; Degradation rate constant CL = TVCL*EXP(ETA(1)) V1 = TVV1*EXP(ETA(2)) Q = TVQ ;*EXP(ETA(3)) V2 = TVV2;*EXP(ETA(4)) KSS = TVKSS;*EXP(ETA(5)) KINT = TVKINT KSYN = TVKSYN KDEG = TVKDEG K = CL/V1 ; elimination rate constant K12 = Q/V1 ; central-tissue rate constant K21 = Q/V2 ;tissue-central rate constant S1 = V1 BASE = KSYN/KDEG ; baseline for target A_0(3) = BASE $DES CONC=0.5*(A(2)/V2-A(3)-KM)+0.5*SQRT((A(2)/V2-A(3)-KM)**2+4*KSS*A(2)/V2) DADT(1) = -(K+K12)*A(1)+K21*CONC*V2 DADT(2) = K12*A(1)- K21*CONC*V2 - KINT*A(3)*CONC*V2/(KSS+CONC) DADT(3) = KSYN - KDEG*A(3) - (KINT-KDEG)*CONC*A(3)/(KSS+CONC) ; CONC = Concentration of free drug in peripheral comp (not measured) ; A1 = Free drug in Central Compart (not measured) ;A2 = Free Drug second compartment amount (not measured) ; A3 = Target (not measured) Although I have written a differential equation for the total drug in peripheral compartment, but I have only measured the free drug concentration in central compartment. I’m not sure how can I write that in the $ERROR block. Any suggestion or help will be gratefully received Regards, Niurys de Castro Suárez -- MSc Niurys de Castro Suárez Profesor Asistente Farmacocinética/Biofarmacia Investigador Agregado Departamento Farmacia Instituto de Farmacia y Alimentos, Universidad de La Habana Cuba "Una estrella brilla en la hora de nuestro encuentro"