Dear NONMEM Users,
I have a study where I'd like to predict AUC based on 2~3 trough
concentrations. There are about 500 subjects and I intend to predict
drug concentration for 560 time points for each subject (10 time
points/day * 56 days). The EBE for model parameters for each individual
have been generated and they will be fed into NONMEM for calculation of
drug concentrations. The following is the relevant NONMEM code:
$INPUT ID DOSE=DROP DAYN TIME AMT DV EVID MDV ADDL II CONC CLI V2I Q3I
V3I Q4I V4I KAI F1I ALGI
$SUBROUTINES ADVAN12 TRANS4
$PK
CL=CLI
V2=V2I
KA=KAI
F1=F1I
Q3=Q3I
V3=V3I
Q4=Q4I
V4=V4I
ALAG1=ALGI
S2=V2I*624.709/1E6
$ERROR
IPRED=F
Y=F
$SIMULATION (26730517) ONLYSIMULATION SUBPROBLEMS=1
But I get error message like
0WARNING: MAXIMUM NUMBER OF THETA'S PLUS VARIANCE COMPONENTS
EXCEEDS MAXIMUM NUMBER OF PARAMETERS THAT CAN BE ESTIMATED.
SEE INSTALLATION GUIDE
I've increased LTH to 60 in file SIZES, LVR has a value of 30, but still
encounter this error message.
Does anybody have done similar thing in the past? What's likely to be
the true issue here? Your suggestion will be greatly appreciated.
Yaming
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Predict AUC based on trough concentrations
Dear Yamin:
This is caused by the 560 time points that exceeded the max limit of
observations. For SIZE_big, the limit is 500 (see the partial codes below
for nm7). You need to change NO=500 to something bigger.
Sam Liao
Pharmax Research
============================================================================
==========
! NO: MAX NO. OF OBSERVATION RECORDS / INDIVIDUAL RECORD
! IF NO IS CHANGED, ALSO RECOMPILE NM-TRAN, NM-TRAN LIBRARY
PARAMETER (NO=500)! TL 4/22/09
Quoted reply history
From: [email protected] [mailto:[email protected]] On
Behalf Of Hang, Yaming
Sent: Wednesday, February 17, 2010 10:23 AM
To: [email protected]
Subject: [NMusers] Predict AUC based on trough concentrations
Dear NONMEM Users,
I have a study where I'd like to predict AUC based on 2~3 trough
concentrations. There are about 500 subjects and I intend to predict drug
concentration for 560 time points for each subject (10 time points/day * 56
days). The EBE for model parameters for each individual have been generated
and they will be fed into NONMEM for calculation of drug concentrations. The
following is the relevant NONMEM code:
$INPUT ID DOSE=DROP DAYN TIME AMT DV EVID MDV ADDL II CONC CLI V2I Q3I V3I
Q4I V4I KAI F1I ALGI
$SUBROUTINES ADVAN12 TRANS4
$PK
CL=CLI
V2=V2I
KA=KAI
F1=F1I
Q3=Q3I
V3=V3I
Q4=Q4I
V4=V4I
ALAG1=ALGI
S2=V2I*624.709/1E6
$ERROR
IPRED=F
Y=F
$SIMULATION (26730517) ONLYSIMULATION SUBPROBLEMS=1
But I get error message like
0WARNING: MAXIMUM NUMBER OF THETA'S PLUS VARIANCE COMPONENTS
EXCEEDS MAXIMUM NUMBER OF PARAMETERS THAT CAN BE ESTIMATED.
SEE INSTALLATION GUIDE
I've increased LTH to 60 in file SIZES, LVR has a value of 30, but still
encounter this error message.
Does anybody have done similar thing in the past? What's likely to be the
true issue here? Your suggestion will be greatly appreciated.
Yaming
Notice: This e-mail message, together with any attachments, contains
information of Merck & Co., Inc. (One Merck Drive, Whitehouse Station, New
Jersey, USA 08889), and/or its affiliates Direct contact information for
affiliates is available at http://www.merck.com/contact/contacts.html) that
may be confidential, proprietary copyrighted and/or legally privileged. It
is intended solely for the use of the individual or entity named on this
message. If you are not the intended recipient, and have received this
message in error, please notify us immediately by reply e-mail and then
delete it from your system.
Yaming
I think you need to have THETAs, ETAs and OMEGAs in the control stream even if you do not use them. Try to add
Y=F+THETA(1)+ETA(1)+EPS(1)
$THETA
0 FIXED
$OMEGA
0 FIXED
$SIGMA
0 FIXED
instead of
Y=F
Also, you can get AUC much easier than by adding 560 points per subject: re-write your system in terms of differential equations and add AUC compartment
$DES
...
DADT(5)=A(2)/S2
Values of A(5) at any time is the AUC from time zero up to the current time
Thanks
Leonid
--------------------------------------
Leonid Gibiansky, Ph.D.
President, QuantPharm LLC
web: www.quantpharm.com
e-mail: LGibiansky at quantpharm.com
tel: (301) 767 5566
Hang, Yaming wrote:
> Dear NONMEM Users,
>
> I have a study where I'd like to predict AUC based on 2~3 trough concentrations. There are about 500 subjects and I intend to predict drug concentration for 560 time points for each subject (10 time points/day * 56 days). The EBE for model parameters for each individual have been generated and they will be fed into NONMEM for calculation of drug concentrations. The following is the relevant NONMEM code:
>
> $INPUT ID DOSE=DROP DAYN TIME AMT DV EVID MDV ADDL II CONC CLI V2I Q3I V3I Q4I V4I KAI F1I ALGI
>
> $SUBROUTINES ADVAN12 TRANS4
>
> $PK CL=CLI
>
> V2=V2I
> KA=KAI
> F1=F1I
> Q3=Q3I
> V3=V3I
> Q4=Q4I
> V4=V4I
> ALAG1=ALGI
> S2=V2I*624.709/1E6
>
> $ERROR
> IPRED=F
> Y=F
>
> $SIMULATION (26730517) ONLYSIMULATION SUBPROBLEMS=1
>
> But I get error message like
> *0WARNING: MAXIMUM NUMBER OF THETA'S PLUS VARIANCE COMPONENTS*
> * EXCEEDS MAXIMUM NUMBER OF PARAMETERS THAT CAN BE ESTIMATED.*
> * SEE INSTALLATION GUIDE*
>
> I've increased LTH to 60 in file SIZES, LVR has a value of 30, but still encounter this error message.
>
> Does anybody have done similar thing in the past? What's likely to be the true issue here? Your suggestion will be greatly appreciated.
>
> Yaming
>
> Notice: This e-mail message, together with any attachments, contains information
> of Merck & Co., Inc. (One Merck Drive, Whitehouse Station, New Jersey, USA
> 08889), and/or its affiliates Direct contact information for affiliates is
> available at http://www.merck.com/contact/contacts.html) that may be confidential,
> proprietary copyrighted and/or legally privileged. It is intended solely for the
> use of the individual or entity named on this message. If you are not the intended
> recipient, and have received this message in error, please notify us immediately by
> reply e-mail and then delete it from your system.
Dear All,
I'm grateful for the many responses that you posted to my question
regarding AUC prediction based on a few trough concentrations.
My final conclusion on this problem is that it is related to the
improper configuration of the SIZES file. Before this large scale
exercise, I did some thing similar with a much small trial (12 subjects
with less than 30 time points each) on my laptop, no problem with that
one at all. The initial error message with the large scale problem (run
on laptop) is about the MAXID parameter in SIZES file. Although I've
increased the value of MAXID and NO parameters and recompiled, there was
still error message. I was told by a colleague that if several other
parameters are not changed accordingly, the issue is not completely
solved. So eventually I run the NONMEM control file on Unix system where
much larger MAXID and NO are allowed, and it worked.
Thanks for your suggestions of adding an AUC compartment, this is
certainly something new I learned.
Kind regards,
Yaming
Quoted reply history
-----Original Message-----
From: Johan Wallin [mailto:[email protected]]
Sent: Thursday, February 18, 2010 9:23 AM
To: Hang, Yaming
Subject: Re: [NMusers] Predict AUC based on trough concentrations
Yaming,
Maybe I misunderstood what you were trying to do here. As I interpret
you
were not simulating and reestimating, but rather just want to calculate
AUC:s based on the EBE parameters from sparse sampling? An easier way
would
be to simply calculate AUC in your original run, i.e. tabulating AUCi
based
on the CLi. That would eliminate the need for this second run, and
resetting the sizes.
/Johan
Johan WALLIN PhD
Research Scientist PK/PD/TS
Lilly UK (Embedded image moved to file:
Erl Wood Manor pic26308.gif)
Windlesham, Surrey, GU20 6PH
UNITED KINGDOM
Tel: +44 1276 483273 Fax: +44
1276 484367
www.lilly.co.uk
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"Hang, Yaming"
<yaming_h...@merc
k.com>
To
Sent by: <[email protected]>
owner-nmus...@glo
cc
bomaxnm.com
Subject
[NMusers] Predict AUC based on
17/02/2010 18:22 trough concentrations
Dear NONMEM Users,
I have a study where I'd like to predict AUC based on 2~3 trough
concentrations. There are about 500 subjects and I intend to predict
drug
concentration for 560 time points for each subject (10 time points/day *
56
days). The EBE for model parameters for each individual have been
generated and they will be fed into NONMEM for calculation of drug
concentrations. The following is the relevant NONMEM code:
$INPUT ID DOSE=DROP DAYN TIME AMT DV EVID MDV ADDL II CONC CLI V2I Q3I
V3I
Q4I V4I KAI F1I ALGI
$SUBROUTINES ADVAN12 TRANS4
$PK
CL=CLI
V2=V2I
KA=KAI
F1=F1I
Q3=Q3I
V3=V3I
Q4=Q4I
V4=V4I
ALAG1=ALGI
S2=V2I*624.709/1E6
$ERROR
IPRED=F
Y=F
$SIMULATION (26730517) ONLYSIMULATION SUBPROBLEMS=1
But I get error message like
0WARNING: MAXIMUM NUMBER OF THETA'S PLUS VARIANCE COMPONENTS
EXCEEDS MAXIMUM NUMBER OF PARAMETERS THAT CAN BE ESTIMATED.
SEE INSTALLATION GUIDE
I've increased LTH to 60 in file SIZES, LVR has a value of 30, but still
encounter this error message.
Does anybody have done similar thing in the past? What's likely to be
the
true issue here? Your suggestion will be greatly appreciated.
Yaming
Notice: This e-mail message, together with any attachments, contains
information of Merck & Co., Inc. (One Merck Drive, Whitehouse Station,
New
Jersey, USA 08889), and/or its affiliates Direct contact information for
affiliates is available at http://www.merck.com/contact/contacts.html)
that
may be confidential, proprietary copyrighted and/or legally privileged.
It
is intended solely for the use of the individual or entity named on this
message. If you are not the intended recipient, and have received this
message in error, please notify us immediately by reply e-mail and then
delete it from your system.
Notice: This e-mail message, together with any attachments, contains
information of Merck & Co., Inc. (One Merck Drive, Whitehouse Station, New
Jersey, USA 08889), and/or its affiliates Direct contact information for
affiliates is available at http://www.merck.com/contact/contacts.html) that may
be confidential, proprietary copyrighted and/or legally privileged. It is
intended solely for the use of the individual or entity named on this message.
If you are not the intended recipient, and have received this message in error,
please notify us immediately by reply e-mail and then delete it from your
system.