Lag time
From yin~y@glaxowellcome.com Thu Mar 20 06:17:23 1997
Subject: Lag time
Dear NONMEMers,
I need some help on a lag time problem with NONMEM. Before adding all those ETAs and dose differences, I used a much simpler model. Here is my NMT file.
$PROB XXXX CONCENTRATION
$INPUT ID AMT TIME DV=CONC
$DATA CMA02_2.TXT
$SUBROUTINE ADVAN4
$PK
KA = THETA(1)
K = THETA(2)*EXP(ETA(1))
K23= THETA(3)
K32= THETA(4)
S2 = THETA(5)*EXP(ETA(2))
S3 = THETA(6)
ALAG1=THETA(7)
$ERROR
Y = F*EXP(EPS(1))
$THETA
(0, 2, 300) ;KA
(0, 0.5,10) ;K
(0, 0.1, 20) ;K23
(0, 0.3,20) ;K32
(0,20, 1000) ;S2
(0,10, 1000) ;S3
(0,0.5,30) ;ALAG1
$OMEGA 50, 50
$SIGMA 100
$EST MAXEVAL=8000 PRINT=10 SIGDIGITS=4 POSTHOC
$COV
$SCAT (RES WRES) VS TIME
$SCAT PRED VS DV UNIT
It gave me an error:
PROGRAM TERMINATED BY OBJ, ERROR IN CELS
WITH INDIVIDUAL 1 (IN INDIVIDUAL RECORD ORDERING)
INTRAINDIVIDUAL VARIANCE OF DATA FROM OBS RECORD 1 ESTIMATED TO BE 0
MESSAGE ISSUED FROM ESTIMATION STEP
AT INITIAL OBJ. FUNCTION EVALUATION
After deleting
ALAG1=THETA(7),
and it's initial value, I got some reasonable estimations for K and Ka, not for others, but it was a big improvement. I knew there was a lag time from WinNonlin, but I am not sure how to use NONMEM to estimate it. Someone advised me that I need to use some statements like `IF lag time ....' but he was not sure how exactly it was or it may not be needed anyway. Could anyone give me some help?
Thanks.
Yin
Here are data for the first two subjects:
1 100 0 0
1 0 0.25 0
1 0 0.5 1.66
1 0 1 3.46
1 0 1.5 3.61
1 0 2 2.87
1 0 3 2.12
1 0 4 1.47
1 0 5.1 1.21
1 0 6 2.07
1 0 8 0.51
1 0 12 0.46
1 0 16 0.2
1 0 24.17 0.11
1 400 672 0
1 0 672.25 0
1 0 672.5 1.77
1 0 673 36.64
1 0 673.5 28.96
1 0 674.08 18.48
1 0 675 15.25
1 0 676 11.66
1 0 677 9.74
1 0 678 6.43
1 0 680 5.27
1 0 682 1.85
1 0 684 2.19
1 0 688 1.12
1 0 696 0.29
2 100 0 0
2 0 0.25 0
2 0 0.5 0.9
2 0 1 2.36
2 0 1.5 2.22
2 0 2 2.05
2 0 3 1.53
2 0 4 1.28
2 0 5 1.13
2 0 6 0.64
2 0 8 0.44
2 0 12 0.17
2 0 16 0.07
2 0 24.22 0
2 400 672 0
2 0 672.25 0.15
2 0 672.5 8.77
2 0 673 15.15
2 0 673.5 12.68
2 0 674 10.62
2 0 675 10.35
2 0 676 6.74
2 0 677.17 6.29
2 0 678 4.09
2 0 680 2.62
2 0 682 3.52
2 0 684 1.13
2 0 688 0.54
2 0 696.03 0.37
2 800 1344 0
2 0 1344.25 0.1
2 0 1344.5 3.41
2 0 1345 14.92
2 0 1345.5 18.86
2 0 1346 18.09
2 0 1347 22.42
2 0 1348 21.05
2 0 1349 16.66
2 0 1350 11.79
2 0 1352 7.95
2 0 1354 4.74
2 0 1356 3.18
2 0 1360 1.06
2 0 1368 0.34