# PK model code **URL:** \ **Category:** Modelling and Simulation\ **Created:** [October 12, 2023, 9:12am UTC](https://forum.certara.com/t/pk-model-code/3708 "2023-10-12T09:12:04Z")\ **Posts on this page:** 1\ **Page:** 1
**Author:** ![18963422692](https://avatars.discourse-cdn.com/v4/letter/1/a4c791/32.png) [@18963422692](https://forum.certara.com/u/18963422692)\ **Post date:** [October 12, 2023, 9:12am UTC](https://forum.certara.com/t/pk-model-code/3708/1 "2023-10-12T09:12:04Z")
Dear all, I’m trying to reproduce the literature（Mechanistically modeling peripheral cytokine dynamics following bispecific dosing in solid tumors DOI: 10.1002/psp4.12928） using NLME, but I’m always failing. Is there a problem with my code? My model code is as follows.I removed peripheral cytokine dynamics.The literature code is attached. Thank you test(){ dosepoint(A1) #deriv(A1 = -(Q_CentralTebentafusp) + (Q_PeripheralTebentafusp) - (CL_CentralTebentafusp) - ((kin\_skin_CentralTebentafusp-kout\_skin_SkinTebentafusp)Central) - ((kin\_tumorCentralTebentafusp-kout\_tumor_TumorTebentafusp)_Central)) deriv(A1 = -(Q_CentralTebentafusp) + (Q_PeripheralTebentafusp) - (CL_CentralTebentafusp) - ((kin\_skin_CentralTebentafusp)Central-(kout\_skinSkinTebentafusp)Skin) - ((kin\_tumorCentralTebentafusp)Central-(kout\_tumorTumorTebentafusp)Tumor)) CentralTebentafusp=A1/Central #d(Central.Tebentafusp)/dt = -(QCentral.Tebentafusp) + (Q_Peripheral.Tebentafusp) - #(CL_Central.Tebentafusp) - ((kin\_skin_Central.Tebentafusp-kout\_skin_Skin.Tebentafusp)Central) - ((kin\_tumorCentral.Tebentafusp-kout\_tumor_Tumor.Tebentafusp)_Central) deriv(A2 = ((Q_CentralTebentafusp) - (Q_PeripheralTebentafusp))) PeripheralTebentafusp=A2/Peripheral #d(PeripheralTebentafusp)/dt = 1/Peripheral_((Q_CentralTebentafusp) - (Q_PeripheralTebentafusp)) deriv(A3 =(-((kon\_CD3_TumorCD3_TumorTebentafusp-koff\_CD3_TumorCD3Tebentafusp)) - ((kon\_gp100_Tumorgp100_TumorTebentafusp-koff\_gp100_Tumorgp100Tebentafusp)) - ((kin\_tumor_CentralTebentafusp-kout\_tumor_TumorTebentafusp)))) TumorTebentafusp=A3 #d(TumorTebentafusp)/dt = 1/Tumor\*(-((kon\_CD3_TumorCD3_TumorTebentafusp- #koff\_CD3_TumorCD3Tebentafusp)Tumor) - ((kon\_gp100Tumorgp100_TumorTebentafusp-koff\_gp100_Tumorgp100Tebentafusp)Tumor) + ((kin\_tumorCentralTebentafusp-kout\_tumor_TumorTebentafusp)_Central)) deriv(A4 =(-((kon\_CD3_TumorCD3_TumorTebentafusp-koff\_CD3_TumorCD3Tebentafusp)) - ((kon\_CD3_Tumorgp100Tebentafusp_TumorCD3-koff\_CD3_TumorTrimer)))) TumorCD3=A4 #d(TumorCD3)/dt = 1/Tumor_(-((kon\_CD3_TumorCD3_TumorTebentafusp- #koff\_CD3_TumorCD3Tebentafusp)Tumor) - ((kon\_CD3Tumorgp100Tebentafusp_TumorCD3-koff\_CD3_TumorTrimer)Tumor)) deriv(A5 =(((kon\_CD3TumorCD3_TumorTebentafusp-koff\_CD3\*TumorCD3Tebentafusp)) - ((kon\_gp100_TumorCD3Tebentafusp_Tumorgp100-koff\_gp100_TumorTrimer)))) TumorCD3Tebentafusp=A5 #d(TumorCD3Tebentafusp)/dt = 1/Tumor_(((kon\_CD3_TumorCD3_TumorTebentafusp- #koff\_CD3_TumorCD3Tebentafusp)Tumor) - ((kon\_gp100TumorCD3Tebentafusp_Tumorgp100-koff\_gp100_TumorTrimer)Tumor)) deriv(A6 =(-((kon\_gp100Tumorgp100_TumorTebentafusp-koff\_gp100_Tumorgp100Tebentafusp)) - ((kon\_gp100_TumorCD3Tebentafusp_Tumorgp100-koff\_gp100_TumorTrimer)))) Tumorgp100=A6 #d(Tumorgp100)/dt = 1/Tumor\*(-((kon\_gp100_Tumorgp100_TumorTebentafusp- #koff\_gp100_Tumorgp100Tebentafusp)Tumor) - ((kon\_gp100TumorCD3Tebentafusp_Tumorgp100-koff\_gp100_TumorTrimer)Tumor)) deriv(A7 =(((kon\_gp100Tumorgp100_TumorTebentafusp-koff\_gp100\*Tumorgp100Tebentafusp)) - ((kon\_CD3_Tumorgp100Tebentafusp_TumorCD3-koff\_CD3_TumorTrimer)))) Tumorgp100Tebentafusp=A7 #d(Tumorgp100Tebentafusp)/dt = 1/Tumor_(((kon\_gp100_Tumorgp100_TumorTebentafusp- #koff\_gp100_Tumorgp100Tebentafusp)Tumor) - ((kon\_CD3Tumorgp100Tebentafusp_TumorCD3-koff\_CD3_TumorTrimer)Tumor)) deriv(A8 = (((kon\_gp100TumorCD3Tebentafusp_Tumorgp100-koff\_gp100_TumorTrimer)) + ((kon\_CD3_Tumorgp100Tebentafusp_TumorCD3-koff\_CD3_TumorTrimer)))) TumorTrimer=A8 #d(TumorTrimer)/dt = 1/Tumor\*(((kon\_gp100_TumorCD3Tebentafusp_Tumorgp100- #koff\_gp100_TumorTrimer)Tumor) + ((kon\_CD3Tumorgp100Tebentafusp_TumorCD3-koff\_CD3_TumorTrimer)Tumor)) deriv(A9 = (-((kon\_CD3SkinCD3_SkinTebentafusp-koff\_CD3\*SkinCD3Tebentafusp)) - ((kon\_gp100_Skingp100_SkinTebentafusp-koff\_gp100_Skingp100Tebentafusp)) + ((kin\_skin_CentralTebentafusp-kout\_skin_SkinTebentafusp)))) SkinTebentafusp=A9 #d(SkinTebentafusp)/dt = 1/Skin_(-((kon\_CD3_SkinCD3_SkinTebentafusp- #koff\_CD3_SkinCD3Tebentafusp)Skin) - ((kon\_gp100Skingp100_SkinTebentafusp-koff\_gp100_Skingp100Tebentafusp)Skin) + ((kin\_skinCentralTebentafusp-kout\_skin_SkinTebentafusp)_Central)) deriv(A10 = (-((kon\_CD3_SkinCD3_SkinTebentafusp-koff\_CD3_SkinCD3Tebentafusp)) - ((kon\_CD3_Skingp100Tebentafusp_SkinCD3-koff\_CD3_SkinTrimer)))) SkinCD3=A10 #d(SkinCD3)/dt = 1/Skin_(-((kon\_CD3_SkinCD3_SkinTebentafusp- #koff\_CD3_SkinCD3Tebentafusp)Skin) - ((kon\_CD3Skingp100Tebentafusp_SkinCD3-koff\_CD3_SkinTrimer)Skin)) deriv(A11 =(((kon\_CD3SkinCD3_SkinTebentafusp-koff\_CD3\*SkinCD3Tebentafusp)) - ((kon\_gp100_SkinCD3Tebentafusp_Skingp100-koff\_gp100_SkinTrimer)))) SkinCD3Tebentafusp=A11 #d(SkinCD3Tebentafusp)/dt = 1/Skin_(((kon\_CD3_SkinCD3_SkinTebentafusp- #koff\_CD3_SkinCD3Tebentafusp)Skin) - ((kon\_gp100SkinCD3Tebentafusp_Skingp100-koff\_gp100_SkinTrimer)Skin)) deriv(A12 = (-((kon\_gp100Skingp100_SkinTebentafusp-koff\_gp100_Skingp100Tebentafusp)) - ((kon\_gp100_SkinCD3Tebentafusp_Skingp100-koff\_gp100_SkinTrimer)))) Skingp100=A12 #d(Skingp100)/dt = 1/Skin\*(-((kon\_gp100_Skingp100_SkinTebentafusp- #koff\_gp100_Skingp100Tebentafusp)Skin) - ((kon\_gp100SkinCD3Tebentafusp_Skingp100-koff\_gp100_SkinTrimer)Skin)) deriv(A13 = (((kon\_gp100Skingp100_SkinTebentafusp-koff\_gp100_Skingp100Tebentafusp)) - ((kon\_CD3_Skingp100Tebentafusp_SkinCD3-koff\_CD3_SkinTrimer)))) Skingp100Tebentafusp=A13 #d(Skingp100Tebentafusp)/dt = 1/Skin\*(((kon\_gp100_Skingp100_SkinTebentafusp- #koff\_gp100_Skingp100Tebentafusp)Skin) - ((kon\_CD3Skingp100Tebentafusp_SkinCD3-koff\_CD3_SkinTrimer)Skin)) deriv(A14 = (((kon\_gp100SkinCD3Tebentafusp_Skingp100- koff\_gp100_SkinTrimer)) + ((kon\_CD3_Skingp100Tebentafusp_SkinCD3-koff\_CD3_SkinTrimer)))) SkinTrimer=A14 #d(SkinTrimer)/dt = 1/Skin\*(((kon\_gp100_SkinCD3Tebentafusp_Skingp100- #koff\_gp100_SkinTrimer)Skin) + ((kon\_CD3Skingp100Tebentafusp_SkinCD3-koff\_CD3\*SkinTrimer)\*Skin)) #dosepoint(A1, idosevar = A1Dose, infdosevar = A1InfDose, infratevar = A1InfRate) error(CEps = 0.018) observe(CObs = CentralTebentafusp \* (1 + CEps)) #Initial Assignments sequence{ TumorCD3 = Tumor\_BL\_Tcell_CD3\_per\_cell/(Avogadro_Tumor) Tumorgp100 = Tumor\_BL\_Tumorcell_gp100\_per\_cell/(Avogadro_Tumor) SkinCD3 = Skin\_BL\_Tcell_CD3\_per\_cell/(Avogadro_Skin) Skingp100 = Skin\_BL\_Melanocyte_gp100\_per\_cell_Skin\_gp100\_ratio/(Avogadro\*Skin) } fixef(Central(freeze) = c(,5.25,)) fixef(Peripheral(freeze) = c(,470,)) fixef(Tumor(freeze) = c(,0.0007,)) fixef(Skin(freeze) = c(,0.26,)) fixef(CL(freeze) = c(,4.33/24,)) fixef(Q(freeze) = c(,11.4/24,)) fixef(kin\_tumor(freeze) = c(,3.73,)) fixef(kin\_skin(freeze) = c(,1.06,)) fixef(kon\_CD3(freeze) = c(,0.026_10^9,)) fixef(koff\_CD3(freeze) = c(,1,)) fixef(kon\_gp100(freeze) = c(,42_10^9,)) fixef(koff\_gp100(freeze) = c(,1,)) fixef(CD3\_per\_cell(freeze) = c(,100000,)) fixef(gp100\_per\_cell(freeze) = c(,100000,)) fixef(Skin\_gp100\_ratio(freeze) = c(,0.01,)) fixef(Tumor\_BL\_Tcell(freeze) = c(,700000,)) fixef(Tumor\_BL\_Tumorcell(freeze) = c(,1.2_10^8,)) fixef(Skin\_BL\_Tcell(freeze) = c(,2_10^9,)) fixef(Skin\_BL\_Melanocyte(freeze) = c(,1.7_10^9,)) fixef(Immune\_cell\_ratio\_to\_Tcell(freeze) = c(,2,)) fixef(kout\_tumor(freeze) = c(,10,)) fixef(kout\_skin(freeze) = c(,10,)) fixef(Avogadro(freeze) = c(,6.02_10^23,)) fixef(molarity(freeze) = c(,1,)) }