Two abosorption periods from a single dose??
From: MATTHEW.HUTMACHER@monsanto.com
Subject: Two abosorption periods from a single dose??
Date: 15 Jan 1999 13:26:16 -0600
Dear all;
I am trying to develop a zero-order absorption 1-compartment open model with two absorption periods, all from the same actual dose. Let the amount of this actual dose be TAMT. My strategy was to use two dose records, each with AMT=TAMT as follows.
# PATNO AMT EVID TIME CONC ABS RATE
8711 100 1 0 . 1 -2
8711 100 1 0 . 2 -2
8711 . 0 0.5 832.0 . .
8711 . 0 1 1400.0 . .
8711 . 0 2 1550.0 . .
8711 . 0 3 1470.0 . .
8711 . 0 4 1720.0 . .
8711 . 0 6 1510.0 . .
8711 . 0 8 1360.0 . .
8711 . 0 12 1060.0 . .
and so on. My NM-TRAN code is:
$INPUT ID AMT EVID TIME DV=CONC ABS RATE
$DATA ***.DAT
$SUBROUTINE ADVAN1 TRANS1
$PK
QABS=0
IF (ABS .EQ. 2) ABS=1
D1 =(1-QCMT)*THETA(1)+QCMT*THETA(2)
K =THETA(3)
V =THETA(4)
ALAG1 =(1-QCMT)*THETA(5)+QCMT*THETA(6)
RT =THETA(7)
F1 =(1-QCMT)*RT+QCMT*(1-RT)
S1=V
etc.
In other words I am putting two doses into CMT=1, where the amounts are AMT*RT and AMT*(1-RT) and the sum is AMT=TAMT. If I fix RT=1 then I believe only one dose should be input with D1=THETA(1) and ALAG1=THETA(5), i.e. THETA(2),THETA(6) should not be implemented, and the model should reduce to the typical zero-order 1-compartment model. Letting MAXEVAL=0 and RT=1, I should only see the effect of one dose (ABS=1) and it should be 100. However the output from the above is:
ID DOSE TIME CONC PRED RES WRES
8711 100 0 0 0 0 0
8711 100 0 0 0 0 0
8711 100 0.5 832 1322.3 -490.3 -845.34
8711 100 1 1400 2692.2 -1292.2 -2228
8711 100 2 1550 5234.9 -3684.9 -6353.3
8711 100 3 1470 4843.4 -3373.4 -5816.3
8711 100 4 1720 4382.5 -2662.5 -4590.5
8711 100 6 1510 3588.1 -2078.1 -3582.9
8711 100 8 1360 8269.1 -6909.1 -11912******
8711 100 12 1060 5543 -4483 -7729.3
(Please ignore the obviously poor starting values). At time=8 (the ***** record) a secondary peak occurs as if the model were seeing the second dose. Am I forgetting something? Please let me know where my mistake is.
Thank you for your time.
Matt