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| TRANSIT COMPARTMENT EXAMPLES |
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A number of examples are provided for the implementation of dose
superimposition into a transit compartment.
BACKGROUND:
These examples are based on the following two papers:
Implementation of a transit compartment model for describing drug
absorption in pharmacokinetic studies
J Pharmacokinet Pharmacodyn (2007) 34:711-726 DOI 10.1007/s10928-007-9066-0
Radojka M. Savic, Daniel M. Jonker, Thomas Kerbusch, Mats. O. Karlsson
Implementation of dose superimposition to introduce multiple
doses for a mathematical absorption model (transit compartment
model)
J Pharmacokinet Pharmacodyn (2012) 39:251-262 DOI 10.1007/s10928-012-9247
Jun Shen, Alison Boeckmann & Andrew Vick
The first paper defines what a transit compartment is, and gives a
model for a single dose into such a compartment. The second paper
gives several ways that multiple dosing with dose superimposition can
be modelled with NONMEM 7.
Files on ftp site and NONMEM 7
The files for the second paper are provided on the IDS ftp site:
ftp://nonmem.iconplc.com/Public/nonmem/transit_compartment/
The same files are also provided with NONMEM 7 in directory
examples\transit_compartment
The general solution (Appendix 4; sumdosetf.ctl) is of particular
interest in that it gives an example of the use of vectors
(e.g., VECTRA(n), VECTRB(n)) and user-written functions (FUNCA,
FUNCB) in abbreviated code.
NEW FILES FOR NONMEM 7:
The following files may be found in the examples directory.
sumdosetn.ctl, sumdosetf.dat
With NONMEM 7, it is also possible to code the general solution
directly in abbreviated code, using the DO WHILE statement, user-
declared arrays, and subscripted variables.
Note that data file sumdosetf.csv is identical to data file
sall6.csv on the ftp site.
As noted in the INTRODUCTION TO NONMEM 7, this includes abbrevi-
ated code for summation such as:
$abbr declare dosetime(100),dose(100)
$abbr declare dowhile i
$DES
INPT=0
I=1
DOWHILE (I<=NDOSE)
IPT=0
IF (T>=dosetime(I)) &
IPT=DOSE(I)*(T-dosetime(I))**NN*EXP(-KTR*(T-dosetime(I)))
INPT=INPT+IPT
I=I+1
ENDDO
ssmultidose.ctl, ssmultidose.dat
This is an example of a steady state reached using multiple tran-
sient bolus doses. The abbreviated code is the same as sum-
dosetn.ctl, but the data file ssmultidose.dat has nine identical
bolus doses, at 12 hour intervals, leading to steady state (to
the number of significant digits printed).
ssonedose.ctl, ssonedose.dat
This is an example of a steady state computed with a single dose
record having SS=1 and II=12. The data file is ssonedose.dat.
The $PK block saves the values of AMT and II from the dose
record. Abbreviated code in the $DES block contains a DO WHILE
loop that adds drug from each implied dose, going back in time
till the amount from the implied dose is negligible.
REFERENCES: Guide Introduction_7
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