From: Daniel MAZUIR florent.mazuir@wanadoo.fr Subject:[NMusers] help needed - nonlinear absorption Date: Tue, July 6, 2004 10:19 am Dear NMusers, I am a trainee from Paris Pharmacy School . I'm currently working on a compound presenting a non linear absorption profile and it would be very helpful for me if you could provide an example of a simple NONMEM control file with the non linearity you would implement for absorption. My compound has a zero order Absorption. If not, could you please just tell me if the code has to be written in $PRED or if it could be run with "only" $PK, $DES and ADVAN6or 8?? Many thanks in advance for your help, Florent. _______________________________________________________ From: "Bachman, William (MYD)" bachmanw@iconus.com Subject: RE:[NMusers] help needed - nonlinear absorption Date: Tue, July 6, 2004 11:33 am Daniel, In general, use $PRED when you have an analytical solution for your model (closed form equations). Use $DES, when your model is in terms of differential equations. You may also "approximate" nonlinear absorption using a standard advan and $PK by making the absorption parameter in your model a function of the dose. I'm not sure whether you were inferrring that your compound has nonlinear absorption or nonlinear kinetics, but, here is an example of a nonlinear model for absorption (saturable absorption) using $DES follows: ;Model Desc: saturable absorption ;Project Name: LIBRARY ;Project ID: PdxPop $PROB RUN# 001 $INPUT ID AMT TIME DV CMT $DATA mm2.csv IGNORE=C $SUBROUTINE ADVAN6 TRANS=1 TOL=3 $MODEL NCOMP=2 COMP=(GUT) COMP=(CENTRAL) $PK VM=THETA(1)*EXP(ETA(1)) KM=THETA(2)*EXP(ETA(2)) CL=THETA(3)*EXP(ETA(3)) V2=THETA(4)*EXP(ETA(4)) S2=V2 $DES DADT(1)=-VM*A(1)/(KM+A(1)) DADT(2)= VM*A(1)/(KM+A(1))-CL*A(2)/V2 $ERROR Y=F + F*ERR(1) $THETA (0,10) ;[VM] (0,1) ;[KM] (0,25) ;[CL] (0,50) ;[V2] $OMEGA 0.04;[P] 0.04;[P] 0.04;[P] 0.04;[P] $SIGMA 0.1 ;[P] $EST MAX=1000 PRINT=5 ;$COV $TABLE ID TIME AMT CMT FILE=MM2.tab William J. Bachman, Ph.D. Manager, Pharmacometrics Research and Development GloboMax® The Strategic Pharmaceutical Development Division of ICON plc 7250 Parkway Drive, Suite 430 Hanover, MD 21076 410-782-2212 bachmanw@iconus.com _______________________________________________________