+--------------------------------------------------------------------+
 |                                                                    |
 |                              ADVAN12                               |
 |                                                                    |
 +--------------------------------------------------------------------+

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

 USAGE:
 $SUBROUTINES [ADVAN=]ADVAN12

 SAMPLE:
 $SUBROUTINE ADVAN12

 DISCUSSION:
 ADVAN12  is a routine in PREDPP's library which implements the kinetic
 equations for the Three Compartment  Linear  Model  with  First  Order
 Absorption.

 Compt.   Function       Initial   On/Off    Dose      Default    Default
 No.                     Status    Allowed   Allowed   for Dose   for Obs.
 1        Depot          Off       Yes       Yes       Yes        No
 2        Central        On        No        Yes       No         Yes
 3        Peripheral 1   On        No        Yes       No         No
 4        Peripheral 2   On        No        Yes       No         No
 5        Output         Off       Yes       No        No         No

 TRANS routines that may be used: TRANS1, TRANS4, TRANS6

 Basic PK parameters with TRANS1:

      K (rate constant of elimination)
      K23 (rate constant from central to peripheral 1)
      K32 (rate constant from peripheral 1 to central)
      K24 (rate constant from central to peripheral 2)
      K42 (rate constant from peripheral 2 to central)
      KA (rate constant of absorption)

 Basic PK parameters with TRANS4: (See TRANS4).

 Basic PK parameters with TRANS6: (See TRANS6).

 Additional PK parameters:

      S1 - Scale for depot compartment
      S2 - Scale for central compartment (also called SC)
      S3 - Scale for peripheral compartment 1
      S4 - Scale for peripheral compartment 2
      S5 - Scale for output compartment (also called S0)
      F1 - Bioavailability for depot compartment
      F2 - Bioavailability for central compartment
      F3 - Bioavailability for peripheral compartment 1
      F4 - Bioavailability for peripheral compartment 2
      R1 - Rate for depot compartment
      R2 - Rate for central compartment
      R3 - Rate for peripheral compartment 1
      R4 - Rate for peripheral compartment 2
      D1 - Duration for depot compartment
      D2 - Duration for central compartment
      D3 - Duration for peripheral compartment 1
      D4 - Duration for peripheral compartment 2
      ALAG1 - Absorption lag for depot compartment
      ALAG2 - Absorption lag for central compartment
      ALAG3 - Absorption lag for peripheral compartment 1
      ALAG4 - Absorption lag for peripheral compartment 2
      F0 - Output fraction (also called F5, FO)
      XSCALE - Time scale
      MTIME(i) - Model event times

 Steady-state subroutines:  SS12, SS6

 Other required user or library routines:

 Library:  EXP3  EXP4

 Notes:

 1    Analytical  second derivatives used with the Laplacian method are
      not obtained with ADVAN12.  Numerical second derivatives must  be
      used.

 2    Can  be  greatly  speeded up if calls to PK can be limited.  (Use
      CALLFL=1 in $PK to call once per IR, and use the CALL  data  item
      to  force  additional  calls  if  and  when necessary; e.g., when
      covariates used in the PK model change.)

 REFERENCES: None.


  
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