Re: Help with ODEs for a time varying clearance
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
Quoted reply history
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