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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.


 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
      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:


      The same files are also provided with NONMEM 7 in directory


      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.


 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

      IF (T>=dosetime(I)) &

 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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