Thanks Niurys for revisiting this. It was discussed quite a lot before. Using T in $DES, as Paolo suggested, is what I always do.
As far as your code / model file is concerned, I somehow like it as long as you will be able to explain in simpler terms to non-pharmacometricians and Physicians what the values mean and implications on situations. Thanks, Simba On Thu, Jul 22, 2021, 4:37 PM Leonid Gibiansky <[email protected]> wrote: > PK block is executed only once per record so CL(TIME) is constant > between records, while in the DES block T (time) changes continuously, > thus implementing time dependence CL(T) exactly rather than > approximately. The rest is fine. > Thanks > Leonid > > On 7/22/2021 4:19 PM, Niurys.CS wrote: > > Dear Leonid, > > Thanks for yor suggestion. I've never thought in that possibility. > > However, I have two questions: > > 1-Why must I write those equations inside $DES? > > 2-Do you think the ODE that I proposed are Ok? > > > > Thank you very much > > > > MSc Niurys de Castro Suárez > > Assistant Professor of Pharmacometrics > > Assistant Research > > Pharmacy Department > > Institute of Pharmacy and Food, > > University of Havana > > Cuba > > > > El 22/07/2021 16:04, "Leonid Gibiansky" <[email protected] > > <mailto:[email protected]>> escribió: > > > > Definition of CL should be moved inside the DES block; other than > > that, looks fine: > > ;---- DES ------ > > $DES > > CL2_TIME = CL2*EXP(-KDES*T) > > CL_TOTAL = CL2_TIME + CL1 ; total clearance > > ... > > > > Thanks > > Leonid > > > > > > On 7/22/2021 3:30 PM, Niurys.CS wrote: > > > > 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 > > > >
