From: "Sreenivasa Rao Vanapalli" <rao@pharm.cpb.uokhsc.edu>
Subject: ADVAN4!!!
Date: Fri, 10 Mar 2000 14:56:55 -0800
Hi everyone
I would like to ask a question. I'm trying to model population data for promethazine in rats using two compartment model. With nonmem I'm using subroutine "ADVAN4" for this model. And I'm getting trouble with this. The error message I'm getting is
" PK PARAMETER FOR K IS NON-POSITIVE"
Control statement I'm using is
$INPUT ID DOSE=AMT TIME CP=DV WT
$DATA IMPMZ
$SUBROUTINES ADVAN4
$PK
KA=THETA(1)*ETA(1)
K23=THETA(2)*ETA(2)
K32=THETA(3)*ETA(3)
K=THETA(4)*ETA(4)
V=THETA(5)*ETA(5)
$ERROR
Y=F*(1+ERR(1))
$THETA (0,5)(0,.8)(0,.2)(0,.1)(0,.8)
$OMEGA BLOCK(5) 1.6 5 22.5 3.74 15 11 0.2 2 1.7 1.2 1.6 8.5 6.3 2.3 5.72
$SIGMA .2
$ESTIMATION MAXEVAL=500 PRINT=5
$COVR
$TABLE ID DOSE WT TIME
$SCAT CP VS TIME
$SCAT PRED VS TIME
$SCAT (RES WRES) VS TIME BY ID
$SCAT PRED VS CP UNIT
Data I'm using is.
1 .5 . . .35
1 . .033 .149 .
1 . .515 .262 .
1 . 1.992 .163 .
2 .5 . . .365
2 . .083 .24 .
2 . .769 .247 .
2 . 3.017 .156 .
3 .5 . . .37
3 . .167 .284 .
3 . 1.004 .188 .
3 . 4.021 .09 .
4 .5 . . .365
4 . .271 .256 .
4 . 1.51 .18 .
4 . 5.942 .102 .
9 .5 . . .31
9 . .033 .168 .
9 . .514 .198 .
9 . 2.031 .147 .
10 .5 . . .315
10 . .083 .209 .
10 . .767 .201 .
10 . 2.986 .119 .
11 .5 . . .32
11 . .167 .245 .
11 . 1.172 .165 .
11 . 3.983 .105 .
12 .5 . . .315
12 . .261 .251 .
12 . 1.538 .17 .
13 .5 . . .37
13 . .033 .158 .
13 . .506 .232 .
13 . 2.01 .221 .
14 .5 . . .385
14 . .083 .257 .
14 . .754 .2 .
14 . 3. .149 .
15 .5 . . .39
15 . .167 .273 .
15 . 1. .198 .
15 . 4.075 .096 .
16 .5 . . .38
16 . .249 .224 .
16 . 1.488 .147 .
16 . 6.125 .066 .
Can anyone help me in this..
thanks
Sreenivasa Rao Vanapalli
College of Pharmacy,
University of oklahoma Health Sciences Center
1110 N.Stonewall
Oklahoma City, OK-73117
Tel:405-271-6484 Extn:47232 (office)
:405-521-0826 (Home)
Fax: 405-271-7505(Office)
ADVAN4!!!
From: LSheiner <lewis@c255.ucsf.edu>
Subject: Re: ADVAN4!!!
Date: Fri, 10 Mar 2000 14:02:51 -0800
SRV,
I haven't tried running your problem so perhaps you really are getting that message, but are you sure? That is, are you sure that in the control stream that gave you the problem you didn't have either of the following:
1. $ESTIMATION ... POSTHOC
2. $ESTIMATION ... METHOD=1 (OR FOCE)
But the main reason I am writing is to alert you and nmusers that there is just no way NONMEM can estimate 10 population variance parameters (a full 5 x 5 cov matrix) with data from only 16 persons, and only ca 3 points/person at that!
You really should use nothing more complicated than
> KA=THETA(1)
> K23=THETA(2)
> K32=THETA(3)
> K=THETA(4)*ETA(1)
> V=THETA(5)*ETA(2)
for starters, with a 2x2 OMEGA.
However, this won't solve the problem you asked about, unfortunately.
LBS.
--
_/ _/ _/_/ _/_/_/ _/_/_/ Lewis B Sheiner, MD (lewis@c255.ucsf.edu)
_/ _/ _/ _/_ _/_/ Professor: Lab. Med., Bioph. Sci., Med.
_/ _/ _/ _/ _/ Box 0626, UCSF, SF, CA, 94143-0626
_/_/ _/_/ _/_/_/ _/ 415-476-1965 (v), 415-476-2796 (fax)
From: Mats Karlsson <Mats.Karlsson@biof.uu.se>
Subject: Re: ADVAN4!!!
Date: Sun, 12 Mar 2000 06:46:26 +0100
Hi Sreenivasa,
In addition to Lewis answer, which I agree with, there is a problem in your code in that you write
KA=THETA(1)*ETA(1)
when you probably mean
KA=THETA(1)*EXP(ETA(1))
and the same for the rest of the parameters.
Mats
--
Mats Karlsson, PhD
Professor of Biopharmaceutics and Pharmacokinetics
Div. of Biopharmaceutics and Pharmacokinetics
Dept of Pharmacy
Faculty of Pharmacy
Uppsala University
Box 580
SE-751 23 Uppsala
Sweden
phone +46 18 471 4105
fax +46 18 471 4003
mats.karlsson@biof.uu.se
From: Luann Phillips <luann@phor.com>
Subject: Re: FW: ADVAN4!!!
Date: Mon, 13 Mar 2000 12:10:55 -0500 (EST)
Sreenivasa Rao Vanapalli,
S2=V is the complete scale parameter for ADVAN4 if the Cp unit is ug/mL, the volume unit is L, and the dose unit is mg.
If the Cp unit is ng/mL, the volume unit is L, and the dose unit is mg then S2=V/1000 is the complete scale parameter. In general, the Cp unit*the scale unit (including volume) should equal to the dose unit.
Luann Phillips
Pharmaceutical Outcomes Research, Inc.
435 Lawrence Bell Dr. Suite #7
Williamsville, NY 14221
(716) 633-3463 ext. 236