Dear Alison:
Thanks for let us know this new feature in nm 6. I have been working on
EHC modeling for single dose as well as multiple dose pk data. I have
some questions on how to use this new feature.
How do we define the FLAG when we also have MTIME(3), MTIME(4), MTIME(5)
and MTIME(6)? We observed one peak after each meals and there were
three meals each day.
Best regards,
Sam Liao
Pharmax Research
Dear Sam and Ayyappa,
The postings that Sam mentioned are obsolete.
The first of the model time examples ("help mtime") suggests a
better technique for modelling EHC using MTIME parameters, as follows:
Enterohepatic Recycling
This fragment of abbreviated code may be used to model EHC. The
transfer of drug from compt. 4 to 1 is controlled by FLAG, which
is 1 between the times specified by MTIME(1) and MTIME(2), and is
0 otherwise.
$PK
MTIME(1)=THETA(8)
MTIME(2)=MTIME(1)+THETA(9)
....
$DES
FLAG=MPAST(1)-MPAST(2)
DADT(1)=-KA*A(1)+K41*A(4)*FLAG
DADT(4)=K1G*A(2)-K41*A(4)*FLAG
....
>From "Intro.to NONMEM VI" guide:
There is a new feature: model event times. These are additional PK
parameters MTIME(i) defined in the PK routine or $PK block. A model
event time, like an absorption lag time, defines a time to which the
system is advanced, but whose value usually cannot be known in advance.
When the time is reached, certain indicator variables are set and a call
to PK is made. At this call PK, DES, AES and ERROR can use the indicator
variables to change some aspect of the system, e.g., a term in a
differential equation, or the rate of an infusion. Thus, a model event
time can be used e.g. to mark the time at which the gall bladder begins
to empty. A model event time could be implemented by using an absorption
lag time, and this is what has been done until now, but doing this is
somewhat clumsy. There may be up to PCT model event times, where PCT is
a new installation parameter defined in SIZES. Its default value is 30.
(See the MTIME and $PK and PRDPK1 and PRDPK2 Help Items and the MODEL
TIME Example)
On Thu, 04 Dec 2008 08:43:59 -0500, "Sam Liao"
<[EMAIL PROTECTED]> said:
Dear Ayyappa:
I think you will find the following nmusers net post useful for your
model. Alison had kindly provided some code for a EHC model.
Best regards, Sam Liao Pharmax Research
===================================================================
*Enterohepatic Recirculation Model <
http://www.cognigencorp.com/nonmem/nm/98oct061998.html>* *|...
|*this compartment to the change-point. Based on these ideas, here's
how I would modify Rik's code. The change also provides for the
termination of *EHC <
http://www.cognigencorp.com/nonmem/nm/98oct061998.html#pgfId=424161>*.
If you want to let *EHC* continue indefinitely, delete compartment 6
and its dose, and the code involving ALAG6. 1) Add 2 more
compartments to $MODEL:*| ...|* /
http://www.cognigencorp.com/nonmem/nm/98oct061998.html/ 05/06/03,
19876 bytes
Dear All,
I am trying to model PK data of a drug and many subjects show double
peaks but even in fasting state. Can we expect EHC in fasting
state? Can anybody provide some coding help in modeling intermittent
episodes of EHC rather than continuous mode?
Thank you.
Regards, Ayyappa Chaturvedula
