Dear Niurys, I have not checked the whole code, but something I spotted as incorrect is the use of TIME.
The variable TIME only changes in a discrete way with the time of events in the dataset (e.g. doses or samples). If you want something truly "continuous" you need to use the variable T and define inside the $DES block all the variables that depend on T (and are therefore time varying). In your case, you should move the equations calculating the CL to $DES and use T instead of TIME. ... ;---- DES ------ $DES CL2_TIME = CL2*EXP((-KDES)*(T)) CL_TOTAL = CL2_TIME + CL1 ; total clearance ... For more info, I'd google TIME vs T DES Nonmem, I think there is a tutorial by Nick about this. I hope this helps. Good luck! Paolo On 22 July 2021 21:41:43 "Niurys.CS" <amaranth...@gmail.com> wrote: CAUTION: This email originated outside the UCT network. Do not click any links or open attachments unless you know and trust the source. Dear nmusers, I'm working on the pharmacokinetics of an antiCD20 mAb; I suspect the clearance of this mAb should be time dependent as rituximab’s clearance do. I tried to model this behavior but I’m not sure if the ODEs are correct. Please can you help? I share part of the code. $SUBROUTINE ADVAN13 TOL=9 $MODEL COMP=(CENTRAL) COMP=(PERIPH1) $PK ;---- STRUCTURAL PARAMETERS ------ TVCL1 = THETA(2) ; system-nonspecific clearance TVV1 = THETA(3) TVQ = THETA(4) TVV2 = THETA(5) TVKDES = THETA(6) ; rate constant of the specific clearance decay TVCL2 = THETA(7) ; time varying clearance at time zero ;---- MU_TRANSFORMATION ------ MU_1 = LOG(TVCL1) MU_2 = LOG(TVV1) MU_3 = LOG(TVQ) MU_4 = LOG(TVV2) MU_5 = LOG(TVKDES) MU_6 = LOG(TVCL2) ;---- INDIVIDUAL PARAMETERS ------ CL1 = EXP(MU_1+ETA(1)) V1 = EXP(MU_2+ETA(2)) Q = EXP(MU_3+ETA(3)) V2 = EXP(MU_4+ETA(4)) KDES = EXP(MU_5+ETA(5)) CL2 = EXP(MU_6+ETA(6)) S1 = V1 ;---- INITIAL CONDITIONS ------ A_0(1) = 0 A_0(2) = 0 CL2_TIME = CL2*EXP((-KDES)*(TIME)) CL_TOTAL = CL2_TIME + CL1 ; total clearance ;---- DES ------ $DES CONC = A(1)/V1 DADT(1) =-(CL_TOTAL/V1)*A(1)-(Q/V1)*A(1)+(Q/V2)*A(2) DADT(2) = (Q/V1)*A(1)-(Q/V2)*A(2) ;----$ERROR ------ CONC1 = A(1)/V1 IPRED=-3 IF(CONC1.GT.0) IPRED=LOG(CONC1) W = THETA(1) Y = IPRED+W*EPS(1) IRES=DV-IPRED IWRES=IRES/W Thank you, Niurys MSc Niurys de Castro Suárez Assistant Professor of Pharmacometrics Assistant Research Pharmacy Department Institute of Pharmacy and Food, University of Havana Cuba Disclaimer - University of Cape Town This email is subject to UCT policies and email disclaimer published on our website at http://www.uct.ac.za/main/email-disclaimer or obtainable from +27 21 650 9111. If this email is not related to the business of UCT, it is sent by the sender in an individual capacity. Please report security incidents or abuse via https://csirt.uct.ac.za/page/report-an-incident.php.
