Q:$DES with a lagged zero-order bolus dose

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)