NONMEM Users Network Archive

Hosted by Cognigen

Re: Code for EHC

From: Alison Boeckmann <alisonboeckmann>
Date: Thu, 04 Dec 2008 09:11:23 -0800

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"
<sliao
> 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
>
--
  Alison Boeckmann
  alisonboeckmann
Received on Thu Dec 04 2008 - 12:11:23 EST

The NONMEM Users Network is maintained by ICON plc. Requests to subscribe to the network should be sent to: nmusers-request@iconplc.com.

Once subscribed, you may contribute to the discussion by emailing: nmusers@globomaxnm.com.