+--------------------------------------------------------------------+
 |                                                                    |
 |                           ADVAN5 ADVAN7                            |
 |                                                                    |
 +--------------------------------------------------------------------+

 MEANING: Choice of Pharmacokinetic Model for PREDPP
 CONTEXT: Option of NM-TRAN $SUBROUTINES record

 USAGE:
 $SUBROUTINES [ADVAN=]ADVAN5

 SAMPLE:
 $SUBROUTINE ADVAN5

 DISCUSSION:
 ADVAN5 and ADVAN7 are routines in PREDPP's library which implement the
 general linear model.  The general linear model is used for systems in
 which  a  drug is distributed between compartments according to linear
 processes.  ADVAN7 may be used when the eigenvalues of the  rate  con-
 stant  matrix are known to be real (which is true for many pharmacoki-
 netic systems such as mammillary models).  It is generally faster than
 ADVAN5.

 A  $MODEL  record  is  required to describe the compartments and their
 attributes.  The $PK record (or, if  a  user-supplied  PK  routine  is
 used, the $MODEL record) describes how the compartments are linked.

 TRANS routines that may be used: TRANS1

 Suppose  there  are m compartments in the system, including the output
 compartment.

 Basic PK parameters with TRANS1:

      Kij (rate constant from compartment i to compartment j)
      Ki0 (alternate name for Kim)

      The letter T may be used as a separator between the two  compart-
      ment numbers, e.g., KiTj.  The letter T is optional when there is
      no ambiguity, but required when there are two possible  interpre-
      tations  of  the  numbers  that follow K.  E.g., with 12 compart-
      ments, K111 is ambiguous.  It should be  coded  K1T11  or  K11T1,
      depending  if  it symbolizes the rate constant from compartment 1
      to compartment 11 or from compartment 11 to compartment 1.

 Additional PK parameters:

 For each compartment n in the system (n=1, ..., m):

      Sn - Scale for nth compartment
      S0 - Alternate name for scale for output compartment

 For each dosable compartment n in the system:

      Fn - Bioavailability for nth compartment
      Rn - Rate for nth compartment
      Dn - Duration for nth compartment
      ALAGn - Absorption lag for nth compartment

 Other additional PK parameters:

      F0 - Output fraction (also called Fm, FO)
      XSCALE - Time scale
      MTIME(i) - Model event times

 Required PREDPP Library subroutines:
 ADVAN5 - REXPON, RXSUBS
 ADVAN7 - RRXPON, RXSUBS

 Notes:

 1    Analytical second derivatives used with the Laplacian method  are
      not  obtained  with  ADVAN5 and ADVAN7.  Numerical second deriva-
      tives must be used.

REFERENCES: Guide VI Section VII.C.5, VII.C.7
REFERENCES: Guide IV Section V.C.4


  
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