RE: Question re: indirect model

From: vgcasabo - vicente.casabo@uv.es Subject: RE: [NMusers] Question re: indirect model Date: 1/7/2004 1:20 PM Dear Jocelyn and Michael Your code and data file has the following problems: You need three compartments to model your data Gut, Pkcentral, Pdcentral Code in CMT variable in your data file: 1(gut), 2(drug concentrations), 3 (biomarker concs.) You do not need any of the IF,THEN,ELSE structures in your $DES model. You have to write DADT(3) differential equation for the biomarker concentration. You need to initialize the third compartment in the data file with AMT=1 at time =0 CMT=3 in additional data records. Then you need another parameter in $PK as F3=THETA(.) and its corresponding ETA(.), KIN and KOUT are then interdependent You need two residuals error models. See the relevant part of model below, I haven't checked it..there might be additional errors. Other parametrization are possible, Hope this helps you. Vicente ------------------------------------------------------------------ ... $MODEL NCOMP=3 COMP=(GUT) COMP=(CENTRAL) COMP= (PDCEN) $PK KA=THETA(1)*EXP(ETA(1)) KE=THETA(2)*EXP(ETA(2)) V2=THETA(3)*EXP(ETA(3)) S2=V2/1000 S3=1 ;or the adequate scale factor F3=THETA(.)*EXP(ETA(.)); To adequate amt to concentration at time cero KIN=KOUT*F3 KOUT=THETA(.)*EXP(ETA(.)) IC50=THETA(6)*EXP(ETA(6)) $DES ;PK MODEL DADT(1)=-KA*A(1) DADT(2)=KA*A(1)-KE*A(2) CP=A(2)/S2 ;PD MODEL EFF=CP/(CP + IC50); EMAX can be necessary, no total inhibition is possible DADT(3)=KIN* (1-EFF)- KIN*A(3) $ERROR ; two residual error models are used IF(CMT.EQ.2) W=EXP(EPS(1)) W=EXP(EPS(2)) Y=F*W IPRED=F _______________________________________________________