RE: ETABAR p-value
Dear Majid,
Since I recently made a similar mistake I can spot one reason for why you only
get a single pulse corresponding to ALAG2. In the INPUT file both does events
(CMT1 & CMT2) have EVID = 4. EVID = 4 leads to reset of the system and the
previous dose record is therefore not taken into account. Change to EVID = 1
and at least one problem is out of the way.
I don't know the nature of your formulation but I think that it in many cases
might also be possible to model this as one single dose and a chain of
absorption compartments. This might be a more physiological approach than to
have two fix doses into two separate absorption compartments.
Kind regards,
Martin Bergstrand, MSc, PhD student
-----------------------------------------------
Division of Pharmacokinetics and Drug Therapy
Department of Pharmaceutical Biosciences
Uppsala University
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P.O. Box 591
SE-751 24 Uppsala
Sweden
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[EMAIL PROTECTED]
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Work: +46 18 471 4639
Mobile: +46 709 994 396
Fax: +46 18 471 4003
Quoted reply history
-----Original Message-----
From: [EMAIL PROTECTED] [mailto:[EMAIL PROTECTED] Behalf Of [EMAIL PROTECTED]
Sent: 22 februari 2007 23:08
To: [email protected]
Subject: RE: [NMusers] ETABAR p-value
Dear NONMEM user,
I appreciate if someone provide me with suggestions regarding the problem
indicated below:
I have been trying to analyze PK data from a dosage form which releases it
content in proximal and distal part of GI tract. Before fitting the model to
my data, I tried to simulate the data. However, I am only getting a single
pulse of a drug with a lag time corresponding to the ALAG2 (lag time for the
second GI compartment). I am wondering if I have errors in my codes or the
data file. Any recommendations greatly appreciated. My control stream and few
lines from the input file are given below:
Control Stream:
;Model Desc: ONE Compartment Model - Double INPUT
;Project Name: XXXX
;Project ID: NO PROJECT DESCRIPTION
$PROB RUN# 1 YOUR TEXT
$INPUT C ID CMT DAT=DROP DATE TIME DV AMT MDV EVID SS II
$DATA POPPK_129V2.CSV IGNORE=C
$SUBROUTINES ADVAN6 TOL=3
$MODEL
COMP=(1) ;(DEPOT1, DEFDOSE)
COMP=(2) ;(DEPOT2)
COMP=(3) ;(CENTRAL,DEFOBS)
$PK
TVCL=THETA(1)
CL=TVCL*EXP(ETA(1))
TVV=THETA(2)
V=TVV*EXP(ETA(2))
TVKA1=THETA(3)
KA1=TVKA1*EXP(ETA(3))
TVKA2=THETA(4)
KA2=TVKA2*EXP(ETA(4))
TVF1=THETA(5)
F1=TVF1
TVLT1=THETA(6)
ALAG1=TVLT1*EXP(ETA(5))
TVLT2=THETA(7)
ALAG2=TVLT2*EXP(ETA(6))
K30=CL/V
IF (F1 .GT. 1) F1=0.999
IF (ALAG1 .LE.0) ALAG1=0
F2=1-F1
S3=V
$DES
RINA=KA1*A(1)
RINB=KA2*A(2)
C3=A(3)/V
DADT(1)=-RINA
DADT(2)=-RINB
DADT(3)=RINA+RINB-K30*A(3)
$ERROR
DEL=0
IF (F.EQ.0) DEL=1
IPRED=F
W=IPRED+DEL
IRES=DV-IPRED
IWRES=IRES/W
Y=F+W*ERR(1)+ERR(2)
$THETA
11000 ;[CL]
21000 ;[TVV]
1 ;[TVKA1]
0.5 ;[TVKA2]
0.25 FIXED ;[TVF1]
0.5 ;[TVLT1]
2.5 ;[TVLT2]
$OMEGA
0 FIXED ;[ETACL]
0 FIXED ;[ETAV]
0 FIXED ;[ETAKA1]
0 FIXED ;[ETAKA2]
0 FIXED ;[ETALT1]
0 FIXED ;[ETALT2]
$SIGMA
0 FIXED ;[ERR1]
0 FIXED ;[ERR2]
;$MSFI
;$EST MAXEVAL=9999 NSIG=3 MSF=1.msf PRINT=5 NOABORT METHOD=0 POSTHOC
;$COVARIANCE
$SIMULATION ONLYSIM (9215690)
$TABLE ID DATE DOSE TIME IPRED CL V KA1 KA2 F1
ALAG2 NOPRINT ONEHEADER FILE=1.TAB
;$TABLE ID CL VC Q VP KA IC50 NOPRINT ONEHEADER FILE=patab43
;$TABLE ID AGE CRCL WT ALB NOPRINT ONEHEADER FILE=cotab1
;$TABLE ID SEX NOPRINT ONEHEADER FILE=catab40
;$TABLE ID TIME IPRED NOPRINT ONEHEADER FILE=sdtab43
INPUT File:
Many Thank,
Majid Vakily, Ph.D.
Senior Research Investigator
Department of Drug Metabolism & Pharmacokinetics
Phone: (847) 582-2198
Fax; (847) 582-2388
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