Dear NMusers,
I am working on a dataset with drug concentration data in both plasma and
urine. I found most of the control streams dealing with urine data
previously posted here were based on user-defined differential equations.
My question is whether a normal ADVAN1 control stream and dataset can be
changed to allow urine data to be used. If so, what has to be change in the
control stream and the dataset? I’d sincerely appreciate it, if somebody
can share with me a sample control stream to simultaneously fit the plasma
and urine data.
Kind regards,
Norman Zhou
Plasma and Urine data
Hi Norman,
I believe that you can use the standard ADVAN routines by putting the urine as
the excretion compartment (e.g. CMT = 3 for ADVAN3). What you would do is:
* Put an EVID=2 with CMT=3 at TIME 0 for each subject (to turn on the
output compartment),
* Put a row with EVID=0, CMT=3, and your observed AMOUNT (not
concentration) of drug in the urine at the end of its observation interval,
* After the EVID=0, CMT=3 row in the above bullet, you need to reset
the compartment to 0 concentration by turning it off then on:
EVID=2, CMT=-3 (note the negative to turn off)
EVID=2, CMT=3 (positive to turn on)
* Then use F3=THETA(X) to estimate the % renal excretion (relative to
F1 bioavailability); set V3=1.
The minimal, more concrete example of the data file is for subject 1 dosed at
time 0 with 5.5 mg measured in the urine at time 4 and 10 mg measured in the
urine at time 12:
ID TIME CMT EVID AMT
# Reset the subject
1 0 . 3 .
# Turn on the urine compartment
1 0 3 2 .
# Dose with 10 mg
1 0 1 1 10
# Any normal intermediate plasma concentration rows should go here.
1 1 2 0 2.2
# Amount in the urine at 4 hours
1 4 3 0 5.5
# Reset and restart the urine compartment
1 4 -3 2 .
1 4 3 2 .
Thanks,
Bill
Quoted reply history
From: [email protected] [mailto:[email protected]] On
Behalf Of Norman Z
Sent: Wednesday, August 08, 2012 4:40 PM
To: [email protected]
Subject: [NMusers] Plasma and Urine data
Dear NMusers,
I am working on a dataset with drug concentration data in both plasma and
urine. I found most of the control streams dealing with urine data previously
posted here were based on user-defined differential equations. My question is
whether a normal ADVAN1 control stream and dataset can be changed to allow
urine data to be used. If so, what has to be change in the control stream and
the dataset? I'd sincerely appreciate it, if somebody can share with me a
sample control stream to simultaneously fit the plasma and urine data.
Kind regards,
Norman Zhou
Hi,
The principle behind using the optional output fraction parameter (FO) that Bill describes below as 'F3' can be found in the NM-HELP (see below). You can use it to estimate renal (CLR) and non-renal clearance (CLNR) as follows:
$PK
CLR=THETA() + ETA()
CLNR=THETA() + ETA()
FO=CLR/(CLR+CLNR)
$ERROR
IF (CMT.EQ.2) Y=A(2)+EPS() ; assuming the output compartment is 2 as it will be if you use ADVAN1
MEANING: Output fraction (F0) parameter for PREDPP
CONTEXT: Additional PK Parameters
USAGE:
$PK
F0= ....
DISCUSSION:
The output fraction parameter is used with PREDPP. It is an optional
additional PK parameter. With NM-TRAN, it are symbolized in the $PK
block by any one of the reserved variables FO, F0, or Fn, where n is
the compartment number of the output compartment.
With any of the kinetic models a (peripheral) output compartment is
always present. Associated with this compartment is a PK parameter,
the output fraction , denoted here by Fo. Of the entire amount, Ao, of
drug introduced into the system by various dosage patterns and then
eliminated from the system during a given time interval, a fraction Fo
of
Ao goes into this output compartment.
If the output compartment is never turned on, the output fraction can
be ignored. If the value of the output fraction is not computed in PK,
it is always understood to be 1
The use of Fo depends on the assumption that the rate of change of
drug amount in the output compartment is linear in the other compart-
ment amounts. Other than this linearity restriction, the system can be
nonlinear.
Good luck,
Nick
Quoted reply history
On 9/08/2012 9:31 a.m., Denney, William S. wrote:
> Hi Norman,
>
> I believe that you can use the standard ADVAN routines by putting the urine as the excretion compartment (e.g. CMT = 3 for ADVAN3). What you would do is:
>
> ·Put an EVID=2 with CMT=3 at TIME 0 for each subject (to turn on the output compartment),
>
> ·Put a row with EVID=0, CMT=3, and your observed AMOUNT (not concentration) of drug in the urine at the end of its observation interval,
>
> ·After the EVID=0, CMT=3 row in the above bullet, you need to reset the compartment to 0 concentration by turning it off then on:
>
> EVID=2, CMT=-3 (note the negative to turn off)
> EVID=2, CMT=3 (positive to turn on)
>
> ·Then use F3=THETA(X) to estimate the % renal excretion (relative to F1 bioavailability); set V3=1.
>
> The minimal, more concrete example of the data file is for subject 1 dosed at time 0 with 5.5 mg measured in the urine at time 4 and 10 mg measured in the urine at time 12:
>
> ID TIME CMT EVID AMT
>
> # Reset the subject
>
> 1 0 . 3 .
>
> # Turn on the urine compartment
>
> 1 0 3 2 .
>
> # Dose with 10 mg
>
> 1 0 1 1 10
>
> # Any normal intermediate plasma concentration rows should go here.
>
> 1 1 2 0 2.2
>
> # Amount in the urine at 4 hours
>
> 1 4 3 0 5.5
>
> # Reset and restart the urine compartment
>
> 1 4 -3 2 .
>
> 1 4 3 2 .
>
> Thanks,
>
> Bill
>
> *From:* [email protected] [ mailto: [email protected] ] *On Behalf Of *Norman Z
>
> *Sent:* Wednesday, August 08, 2012 4:40 PM
> *To:* [email protected]
> *Subject:* [NMusers] Plasma and Urine data
>
> Dear NMusers,
>
> I am working on a dataset with drug concentration data in both plasma and urine. I found most of the control streams dealing with urine data previously posted here were based on user-defined differential equations. My question is whether a normal ADVAN1 control stream and dataset can be changed to allow urine data to be used. If so, what has to be change in the control stream and the dataset? I’d sincerely appreciate it, if somebody can share with me a sample control stream to simultaneously fit the plasma and urine data.
>
> Kind regards,
>
> Norman Zhou
--
Nick Holford, Professor Clinical Pharmacology
First World Conference on Pharmacometrics, 5-7 September 2012
Seoul, Korea http://www.go-wcop.org
Dept Pharmacology & Clinical Pharmacology, Bldg 505 Room 202D
University of Auckland,85 Park Rd,Private Bag 92019,Auckland,New Zealand
tel:+64(9)923-6730 fax:+64(9)373-7090 mobile:+64(21)46 23 53
email: [email protected]
http://www.fmhs.auckland.ac.nz/sms/pharmacology/holford
See also
NONMEM Users Guide - Part V Introductory Guide
Chapter 7 - $SUBROUTINE Record and $PK Record
4.3.3. Scaling by a Data Item
Quoted reply history
On Wed, Aug 8, 2012, at 02:31 PM, Denney, William S. wrote:
Hi Norman,
I believe that you can use the standard ADVAN routines by putting the
urine as the excretion compartment (e.g. CMT = 3 for ADVAN3). What you
would do is:
· Put an EVID=2 with CMT=3 at TIME 0 for each subject (to turn
on the output compartment),
· Put a row with EVID=0, CMT=3, and your observed AMOUNT (not
concentration) of drug in the urine at the end of its observation
interval,
· After the EVID=0, CMT=3 row in the above bullet, you need to
reset the compartment to 0 concentration by turning it off then on:
EVID=2, CMT=-3 (note the negative to turn off)
EVID=2, CMT=3 (positive to turn on)
· Then use F3=THETA(X) to estimate the % renal excretion
(relative to F1 bioavailability); set V3=1.
The minimal, more concrete example of the data file is for subject 1
dosed at time 0 with 5.5 mg measured in the urine at time 4 and 10 mg
measured in the urine at time 12:
ID TIME CMT EVID AMT
# Reset the subject
1 0 . 3 .
# Turn on the urine compartment
1 0 3 2 .
# Dose with 10 mg
1 0 1 1 10
# Any normal intermediate plasma concentration rows should go here.
1 1 2 0 2.2
# Amount in the urine at 4 hours
1 4 3 0 5.5
# Reset and restart the urine compartment
1 4 -3 2 .
1 4 3 2 .
Thanks,
Bill
From: [email protected]
[mailto:[email protected]] On Behalf Of Norman Z
Sent: Wednesday, August 08, 2012 4:40 PM
To: [email protected]
Subject: [NMusers] Plasma and Urine data
Dear NMusers,
I am working on a dataset with drug concentration data in both plasma
and urine. I found most of the control streams dealing with urine data
previously posted here were based on user-defined differential
equations. My question is whether a normal ADVAN1 control stream and
dataset can be changed to allow urine data to be used. If so, what has
to be change in the control stream and the dataset? I’d sincerely
appreciate it, if somebody can share with me a sample control stream to
simultaneously fit the plasma and urine data.
Kind regards,
Norman Zhou
--
Alison Boeckmann
[email protected]
Dear NMusers,
I sincerely appreciate for your kind suggestions.
Kind regards,
Norman Zhou