How to put target baseline inTMDD MODEL in Phoenix

Phoenix Certara Forums Modelling and Simulation
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Dear Experts, I am performing a Target Mediated Drug Disposition (TMDD) Fitting in Phoenix for single dose IV PK data of total drug, target and total target. I am running in a problem with incorporating target baseline value in TMDD model code in Phoenix. I am giving initial dose point for total drug… how to put initial condition for target and total taget…which is equal to baseline. Code is given below; test(){ deriv(TotDrug = - keDrug-kmComp-k12Drug+k21Peri) deriv(Target = kin-koutTarget -konDrugTarget+koffComp) deriv(TotTarget= kin-koutTarget-kmComp) deriv(Peri = k12Drug-k21Peri) Drug=TotDrug-TotTarget+Target Comp=TotTarget-Target dosepoint(TotDrug) Drug=TotDrug/V Looking forward to hear your opinion… Thanks Raj

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Dear Raj Initial conditions for state variables like Target can be done through the sequence statement test(){ deriv(TotDrug = - keDrug-kmComp-k12Drug+k21Peri) deriv(Target = kin-koutTarget -konDrugTarget+koffComp) deriv(TotTarget= kin-koutTarget-kmComp) deriv(Peri = k12Drug-k21Peri) Drug=TotDrug-TotTarget+Target Comp=TotTarget-Target dosepoint(TotDrug) Drug=TotDrug/V sequence {Target=Target0} and you can define Target0 as a structural parameter like kin, kout Best Serge

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Thanks Dr Serg for helping me out. Sequence staement is helping to capture initial baseline value of total target, but total target is not going down and it start increasing from baseline. I check code is correct, seems some error with dosepoint and conversion in concentration term. test(){ deriv(TotDrug = - keDrug-kmComp-k12Drug+k21Peri) deriv(Target = kin-koutTarget -konDrugTarget+koffComp) deriv(TotTarget= kin-koutTarget-kmComp) deriv(Peri = k12Drug-k21Peri) Drug=TotDrug-TotTarget+Target Comp=TotTarget-Target dosepoint(TotDrug) Drug=TotDrug/V sequence {Target=BSL} sequence {TotTarget=BSL} error(TotDrugEps = 1) error(TargetEps = 1) error(TotTargetEps = 1) observe(TotDrugObs = Drug + TotDrugEps) observe(TargetObs = Target + TargetEps) observe(TotTargetObs = TotTarget + TotTargetEps) kon=2.5 kin=kout*BSL BSL=10

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Dear Raj You had some errors in your coding. I fixed those. I suggest you trying this code as an example and let me know if it helps. Best Regards; Serge test(){ deriv(TotDrug = - keDrug-kmComp-k12Drug+k21Peri) deriv(Target = kin-koutTarget -konDrugTarget+koffComp) deriv(TotTarget= kin-koutTarget-kmComp) deriv(Peri = k12Drug-k21Peri) Drug=TotDrug-TotTarget+Target Comp=TotTarget-Target ke=1 km=1 k12=1 k21=1 kout=1 koff=1 V=1 dosepoint(TotDrug) Drug=TotDrug/V # only one sequence where you define the 2 initial conditions with ; as separator sequence {Target=BSL; TotTarget=BSL} error(TotDrugEps = 1) error(TargetEps = 1) error(TotTargetEps = 1) observe(TotDrugObs = Drug + TotDrugEps) observe(TargetObs = Target + TargetEps) observe(TotTargetObs = TotTarget + TotTargetEps) # BSL must be defined before kin BSL=10 kon=2.5 kin=kout*BSL }

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Dear Dr Serge, Thank you so much for your help. It works for me. Regards raj