From: "HUTMACHER, MATTHEW" <MATTHEW.HUTMACHER@chi.monsanto.com>
Subject: ? Emptying the Gall Bladder in NONMEM
Date: Wed, 13 Oct 1999 13:03:55 -0500
> Hello All,
>
> I have an interesting problem, which some of you may have previously
> solved. Any insight or help would greatly be appreciated. I am trying to
> mimic gall bladder filling and emptying. My problem is:
>
> I have a three compartment model open model. It is probably easier to
> write out the differential equations rather than to use English. Let (.)
> represent differentiation with respect to time, k01 is a zero-order input,
> k12 the rate of distribution to the gall bladder compartment, k31 is the
> rate from CMT 3 to CMT 1, k30 is the rate of elimination. The equations
> are:
>
> i) (A1)= k01-k12*R1+k31*R3
> ii) (A2)= k12*R1 -S
> iii) (A3)= -k31*R3+S-k30*R3
>
> S is a function to mimic gall bladder emptying and should have the
> following properties: CMT 2 (gall bladder) is filled by CMT 1 until a
> specified time then all of CMT 2 is emptied as a bolus into CMT 3. S
> needs to be defined as the total amount in CMT 2 at the point of this
> bolus emptying (note: if it is not the system will go to infinity). At
> steady-state S will be the same at each emptying, but when the system is
> initiated, S will be dependent on time and so S will be S=S(t). That is,
> S(t) will depend on the results of the integration of the equations since
> the last emptying. My problem is how to code this in NONMEM. Can one use
> dummy bolus doses into CMT 3 where the bioavailability fraction F3 is set
> to the amount A2 at the time of dumping and simultaneously reset the about
> in CMT 2 equal to 0? I am not sure that it is possible to link the thetas
> in the $PK block with a result from the $DES block.
>
> Any help will be greatly appreciated including other approaches to this
> problem.
> Thank you.
>
> Matt