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 |                                                                 |
 |                                ADVAN9                           |
 |_________________________________________________________________|

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

 USAGE:
 $SUBROUTINES [ADVAN=]ADVAN9

 SAMPLE:
 $SUBROUTINE ADVAN9

 DISCUSSION:
 ADVAN9 is a routine in PREDPP's library which implements  the  general
 non-linear  model  with  equilibrium  compartments.  This general non-
 linear model is used for  systems  in  which  a  drug  is  distributed
 between   compartments   according   to   a   system   of  first-order
 differential-algebraic processes.  It may be useful  when  the  system
 consists  of  only  stiff  differential  equations,  and  there are no
 equilibrium compartments (i.e., no algebraic equations).  It may  also
 be used when the system consists of only algebraic equations (i.e., no
 differential equations).

 A $MODEL record is required to describe  the  compartments  and  their
 attributes.   The $DES record describes the differential equations, if
 any.  The $AES and $AESINITIAL records describe the algebraic  expres-
 sions, if any.

 TOL is required; (See $SUBROUTINES).

 TRANS routines that may be used: TRANS1

 Explicit Basic PK parameters:

   P(n) (nth basic PK parameter)

 Implicit basic PK parameters:

   PK-defined variables used also in $AES or $DES blocks

 Additional PK parameters:

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

 The user may find that the TOL option of the  $SUBROUTINE  record  (or
 the  $TOL  record)  should  specify  larger  NRD values than for other
 ADVANs (e.g., ADVAN6).  Values of 7 or 8 may not be unreasonable  with
 double precision.

 If there is a period of time during which  some  compartment's  amount
 should  be  zero,  that  compartment should be turned off.  Otherwise,
 very small amounts can appear in the compartment, which can cause dif-
 ficulties during subsequent time periods.

 By default, the initial conditions  (i.e.,  compartment  amounts)  are  |
 zero  at the start of each individual record. Different initial condi-  |
 tions may be specified using a compartment initialization block in PK.  |
 When  endogenous drug is specified in the differential equations, non-  |
 zero initial conditions can be  computed  using  a  steady-state  dose  |
 event  record  with SS>0 and AMT=0 and RATE=0, or using the I_SS (Ini-  |
 tial Steady State) feature of MODEL and/or PK.                          |
 (See Compartment Initialization Block, SS dose).                        |
 (See $model, $pk, model, pk, prdpk4).                                   |

 Required PREDPP Library subroutines:
 ADVAN9 - ADDA, FCN5, JAC, LEQT22, LSODI1, LUREF2, RES, ZSPOW2

REFERENCES: Guide VI Section VI.B, VII.C.9
REFERENCES: Guide IV Section V.C.8


  
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