From: MATTHEW.HUTMACHER@monsanto.com
Subject: Q:$DES with a lagged zero-order bolus dose
Date: 24 Jun 1998 16:45:53 -0500
Dear NONMEM users:
I am trying to use ADVAN6 to model a zero-order bolus dose with a lag time. I am having difficulty figuring out how to do this. (I know I could do this with ADVAN3 but there are other modeling issues which require the differential equation solver.)
The code I have been using (obviously wrong) is like the following:
$INPUT ID AMT EVID TIME DV=LCON RATE (rate=-2 duration)
$SUBROUTINE ADVAN6 TRANS1 TOL=5
$MODEL COMP=(CENTRAL,DEFDOSE,DEFOBS)
$PK
CALLFL=-2 (for lagged dose call to PK)
D1 =THETA(1)*EXP(ETA(1))
K12 =THETA(2)*EXP(ETA(2))
K21 =THETA(3)*EXP(ETA(3))
K =THETA(4)*EXP(ETA(4))
V =THETA(5)*EXP(ETA(5))
ALAG1 =THETA(6)*EXP(ETA(6))
S1=V
$DES
Z=0
IF (T.LE.DOSTIM) Z=1
DADT(1)=Z*???-(K12+K)*A(1)
DADT(2)=K12*A(1)-K21*A(2)
Q:$DES with a lagged zero-order bolus dose
From: alison@c255.ucsf.EDU (ABoeckmann)
Subject: Re: Q:$DES with a lagged zero-order bolus dose
Date: 29 Jun 1998 18:30:39 -0400
With ADVAN6, dosing is handled the same as with ADVAN3 (or any other ADVAN routine). Include a dose record with the AMT and the RATE data items, setting RATE to -2. This indicates that D1 will be modelled in $PK, as was done. In the $DES block, code only the compartmental kinetics.
PREDPP itself adds an extra term to DADT(1) giving the total rate of infusion into the compartment (in this case, AMT/D1) when appropriate:
starting when time = ALAG1, and ending when the given AMT has been entered into the system.
The $DES block should be simply:
$DES
DADT(1)=-(K12+K)*A(1)
DADT(2)=K12*A(1)-K21*A(2)
Alison Boeckmann