From: Martin P jedimart2004@yahoo.com
Subject: [NMusers] "First-pass" 3-compartment model
Date: Tue, August 10, 2004 8:41 am

NM users,

Is there a control routine & model out there for a "first-pass"
three-compartment open model (ie. elimination from the second
peripheral compartment rather than the central)?  If not, I have a
specific formula for it that I'd like NONMEM to try and form estimates
with, but am unsure of how to write the proper routine.

Any help is greatly appreciated.
Martin
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From: Luann Phillips luann.phillips@cognigencorp.com
Subject: RE:[NMusers] "First-pass" 3-compartment model
Date: Wed, August 11, 2004 6:47 pm

Martin,

There is not a standard ADVAN for this type model. If the system is
linear, you could implement it with ADVAN5. If you have any nonlinearity
then you would need to use ADVAN6.

Example:

Oral Drug(dose to depot) with first order absorption to the central
compartment and elimination from the peripheral cmt.

 $PROB  3 cmt model with elim from peri
 $INPUT <>
 $DATA  <>
 $SUBROUTINES  ADVAN5
 $MODEL COMP=(DEPOT,INITIALOFF,DEFDOSE) ;cmt=1
        COMP=(CENTRAL)                  ;cmt=2
        COMP=(PERI)                     ;cmt=3
 $PK
   KA=THETA(1)*EXP(ETA(1))
   CL=THETA(2)*EXP(ETA(2))
   Q=THETA(3)*EXP(ETA(3))
   VC=THETA(4)*EXP(ETA(4))
   VP=THETA(5)*EXP(ETA(5))

   S2=v2/1000;   

;ADVAN5 expects Kij parameters where i=cmt number where flow originates
; j=cmt number where flow stops and 0=outside the system
; Note the following equations are just to demonstrate that you can
; still model macro parameters in ADVAN5 as long as you provide the 
; equations for the micro rate constants.
; For ease of demonstration, the equations below are similar to those 
; for a standard 2 cmt model with elimination from the central.
; I have not checked whether they are appropriate for a 2 cmt model with 
; elimination from the peripheral.
   K12=KA     ;flow from depot to central
   K23=Q/VC   ;flow from central to peri
   K32=Q/VP   ;flow from peri to central
   K30=CL/VP  ;elimination from peri

$ERROR

same as usual

Regards,

Luann
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