From: "Mike Cole" <Michael.Cole@newcastle.ac.uk>
Date: Wed, 13 Sep 2000 19:16:47 GMT0BST
Subject: Initial conditions for amounts in compartments
Hello please can you help me? Briefly, I am trying to model the autoinduction of drug clearance using an enzyme turnover model. The model has 3 compartments and is defined in terms of 3 differential equations; I am using ADVAN9. I would like to be able to set the amount in compartment 3, the 'enzyme compartment' equal to 1 and then let the amount change acording to the diff eqns. I have tried
$AESINITIAL
IF (TIME.EQ.0)THEN
A(3)=1
ENDIF
but this does not seem to work. Can you advise me.
Many thanks.
Mike Cole
PS. The control file for the model is below:
$SUBROUTINE ADVAN9 TOL=5
$MODEL NCOMPARTMENTS=3 COMP=(CENTRAL DEFOBSERVATION
DEFDOSE) COMP=(METAB NODOSE) COMP=(ENZIM NODOSE)
$PK
V = THETA(1)
CL = THETA(2)
CLM = THETA(3)
KIN = THETA(4)
KOUT = THETA(5)
$AESINITIAL
IF (TIME.EQ.0)THEN
A(3)=1
ENDIF
$ERROR
IF (CMT.EQ.1) THEN
Y=F+EPS(1)
ELSE
Y=F+EPS(2)
ENDIF
$DES
DADT(1)= - (CL/V) * (A(3)/V) * A(1)
DADT(2)= (CL/V)*(A(3)/V)*A(1) - CLM*A(2)/V
DADT(3)= KIN*A(1) - KOUT*A(3)
________________________________________________
Michael Cole
Department of Statistics,
Merz Court, University of Newcastle upon Tyne,
Newcastle upon Tyne, NE1 7RU, UK
Tel: 0191 222 7209
Fax: 0191 222 8020
Initial conditions for amounts in compartments
From: Nick Holford <n.holford@auckland.ac.nz>
Subject: Re: Initial conditions for amounts in compartments
Date: Thu, 14 Sep 2000 06:43:29 +1200
Mike,
You have run across one of the strange idiosyncrasies of the PREDPP library in NONMEM. Because PREDPP was designed to "do pharmacokinetics" the DE solving component is built to only allow setting of initial conditions by the AMT data item. The work around is simple although tedious because it involves modifying the data set.
You will need to supply a CMT data item in addition to AMT. At the start of each individual set of data records insert a record with TIME=0, CMT=3 and AMT=1. At the times of doses into the CENTRAL compartment you should set CMT=1. PREDPP will then initialize the ENZIM compartment to 1.
A further trick is required if you wish to estimate the initial amount in such a compartment. You can do this by estimating the bioavailability into that compartment e.g.
F3=THETA(x)
where F3 is the bioavailability into compartment 3. F3 is a special name known to PREDPP. There are no inbuilt constraints on F3 (except perhaps it must be non-negative) so you can estimate initial conditions that are > 1.
Nick
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, Private Bag 92019, Auckland, New Zealand
email:n.holford@auckland.ac.nz tel:+64(9)373-7599x6730 fax:373-7556
http://www.phm.auckland.ac.nz/Staff/NHolford/nholford.htm