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
