How does TIME work for multiple doses in NONMEM?
Hi, NM users,
I have a simple question about how TIME works for multiple doses in NONMEM.
Here is my model:
1-CM with dual absorption process (based on a LAG variable)
IOV is also modeled.
Dose regimen: TID doses at 400 mg
Here is the part of dataset:
C ID TIME DOSE DV CMT EVID MDV AMT WT
1 0 400 . 1 1 1 400 70
1 0 400
2 0 0
70
1 0.25 400 240 2 0 0
70
1 0.5 400 410 2 0 0
70
1 4 400 1420 2 0 0
70
1 6 400 820 2 0 0
70
1 7.9 400 450 2 0 0
70
1 8 400 . 1 1 1 400 70
1 8.25 400 240 2 0 0
70
1 8.5 400 410 2 0 0
70
1 12 400 1420 2 0 0
70
1 14 400 820 2 0 0
70
1 15.6 400 450 2 0 0
70
1 16 400 . 1 1 1 400 70
......................................................
Here is the part of NONMEM control stream:
$PROB PK-TEST
$DATA PK-all.csv IGNORE = C
$INPUT C,ID,TIME,DOSE,DV,CMT,EVID,MDV,AMT,WT
$SUBROUTINE ADVAN2 TRANS2
$PK
OCC1=0
OCC2=0
OCC3=0
OCC4=0
OCC5=0
IF(TIME.LE.12) OCC1=1
IF(TIME.GT.12.AND.TIME.LE.24) OCC2=1
IF(TIME.GT.24.AND.TIME.LE.300) OCC3=1
IOV1=OCC1*ETA(4)+OCC2*ETA(5)+OCC3*ETA(6)
IOV2=OCC1*ETA(9)+OCC2*ETA(10)+OCC3*ETA(11)
TKA1= THETA(3)*DEXP(ETA(1))
TKA2= THETA(5)*DEXP(ETA(2))
LAG=0.75
FLAG=0
IF(TIME.GT.LAG) FLAG=1
TVKA=(1-FLAG)*TKA1 + FLAG*TKA2
........
I highlighted TIME in the code, and my question is that when NONMEM hits LAG,
is TIME reseted? (TIME will start from zero for each dose?) Otherwise, after
0.75 hr, FLAG (even for second dose (0-0.75hr)) will be always equal to 1.
Secondly, during IOV calculation, is TIME relative time to the first dose?
It is really confusing me in the code since the same name, TIME, was used here.
Thanks in advance.
Jian
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