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??

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
\$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

\$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
_______________________________________________________