+--------------------------------------------------------------------+
| |
| ADVAN9_15 |
| |
+--------------------------------------------------------------------+
MEANING: Choice of Pharmacokinetic Model for PREDPP
CONTEXT: Option of NM-TRAN $SUBROUTINES record
USAGE:
$SUBROUTINES [ADVAN=]ADVAN9
$SUBROUTINES [ADVAN=]ADVAN15
SAMPLE:
$SUBROUTINE ADVAN9
$SUBROUTINE ADVAN15
DISCUSSION:
ADVAN9 and ADVAN15 are routines in PREDPP's library which implement
the general non-linear model with equilibrium compartments. This gen-
eral non-linear model is used for systems in which a drug is distrib-
uted between compartments according to a system of first-order differ-
ential-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 - Time scale
MTIME(i) - Model event times
With NONMEM 7.4, ATOL may be specified for ADVAN9 and ADVAN15. TOL
(relative tolerance) and ATOL (Absolute tolerance) may be specified on
the $SUBROUTINE record, the $TOL record, or by a user-supplied TOL
subroutine. See also the ATOL option of the $ESTIMATION and $COVARI-
ANCE records.
ATOL is not required. The default is 12 (that is, accuracy is
10**(-12)). Usually the problem runs quickly when using this setting.
On occasion, however, you may want to reduce ATOL (usually set it
equal to that of TOL), and improve speeds of up to 3 to 4 fold.
With ADVAN9, the user may find that the TOL option should specify
larger NRD values than for other ADVANs (e.g., ADVAN6). Values of 7
or 8 may not be unreasonable.
Reserved variable MXSTEP (the maximum number of integration steps)
can be specified for ADVAN9 and ADVAN15, as well as for ADVAN13 and
ADVAN14.
(See mxstep).
With ADVAN9, if there is a period of time during which some compart-
ment's amount should be zero, that compartment should be turned off.
Otherwise, very small amounts can appear in the compartment, which can
cause difficulties 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 provided 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. Note that with either
method, steady-state is computed only for compartments specified by
differential equations. The equilibrium compartments are not computed
(i.e., the algebraic equations are not evaluated) until the system is
advanced beyond the initial value of TIME.
(See Compartment_Initialization_Block, SS_dose).
(See $model, $pk, model, pk).
(See Initial_Steady_State:_I_SS,ISSMOD).
ADVAN9 uses the Lawrence Livermore National Laboratory (LLNL) solver
for differential-algebraic equations, implicit form (LSODI), using the
backward differentiation formulas (BDF) for stiff problems.
ADVAN15 uses IDA from the LLNL SUNDIALS system for differential-alge-
braic equations and is a descendent of the LSODI1 (ADVAN9) system.
ADVAN15 also has a root-finding algorithm. The user may choose to
make modifications to parameters in ..\pr\IDAU.f90.
See ..\guides\idas_guide.pdf and ..\guides\ida_guide.pdf.
See INTRODUCTION TO NONMEM 7, section "$SUBROUTINES: Yet Another New
Differential Equation Solving Method: IDAS (ADVAN15)"
Required PREDPP Library subroutines:
ADVAN9 - ADDA, FCN5, JAC, LEQT22, LSODI1, RES, ZSPOW2
ADVAN15 - ADDA, FCN5, JAC, LEQT22, IDA, RES, ZSPOW2
1 Analytical second derivatives used with the Laplacian method are
not obtained with ADVAN9 and ADVAN15. Numerical second deriva-
tives must be used.
REFERENCES: Guide VI Section VI.B, VII.C.9
REFERENCES: Guide IV Section V.C.8
Go to main index.
Created by nmhelp2html v. 1.0 written by Niclas Jonsson (Modified by AJB 5/2006,11/2007,10/2012)