+--------------------------------------------------------------------+
| |
| $DES |
| |
+--------------------------------------------------------------------+
MEANING: Marks the beginning of abbreviated code for the DES routine
CONTEXT: NM-TRAN Control Record
USAGE:
$DES
abbreviated code
SAMPLE:
Suppose differential equations were used for ADVAN2, rather than the
analytic solution. The $DES block would be as follows:
$DES
DADT(1)=-P(3)*A(1)
DADT(2)=P(3)*A(1)-P(1)*A(2)
DISCUSSION:
The $DES record is used to compute differential equations. It is used
with PREDPP's general non-linear models (ADVAN6, ADVAN8, ADVAN9,
ADVAN13, ADVAN14, ADVAN15, ADVAN16, ADVAN17,ADVAN18). General rules
for abbreviated code are documented elsewhere
(See abbreviated code).
Specific rules follow.
ASSIGNMENT AND CONDITIONAL STATEMENTS
Left-hand quantities in assignment statements:
DADT(1), DADT(2), ... (Required. Derivative of each compartment
amount with respect to time.)
It is important to note that PREDPP itself adds in the rates for
any infusions that may be active. It is possible to introduce
endogenous drug into a compartment by explicit terms in a differ-
ential equation, rather than by PREDPP dose event records. Drug
introduced in this manner is not included by PREDPP in the compu-
tation of the output compartment.
DES-defined (i.e., PRED-defined) items.
Right-hand quantities in assignment statement and in conditions:
A(1), A(2), ... (Current compartment amounts; may be random vari-
ables.)
P(1), P(2), ... (Post-translation explicit basic PK parameters;
may be random variables.)
PK-defined items (Post-translation implicit basic PK parameters; may
be random variables.)
T (Time; may be random variable. T takes values continuously over an |
integration interval.) (Note that T may take values that are larger |
than the ending time of the interval.)
DES-defined items that appeared earlier as left-hand quantities in
$DES.
Data item labels specified on the $INPUT statement may be used
explicitly in DES and $DES abbbreviated code (rather than obtained
as PK parameters). This may improve run time. As with $PK, values
are those of the current event record (the event record to which the
system is being advanced).
THETA(n).
Fortran functions that are continuous, such as SIN and COS, may be |
used. The INT, MOD, and ABS functions (or other functions that intro- |
duce a discontinuity) should not be used in the $DES block. Instead, |
use model event times MTIME in the $PK block, and either set flag |
variables in $PK that can be tested in $DES, or use MPAST in the $DES |
block. See Appendix 3 of Guide VI PREDPP. Several examples are |
available for the use of MTIME with $DES.
(See mtime, model time examples).
(See Examples Using MTIME to Model Periodic Discontinuities in $DES).
See step_circexa.ctl in the NONMEM examples directory.
See idr_circexa.ctl in the NONMEM examples directory.
Global Variables in Modules
Certain variables in FORTRAN Modules can be used.
(See Variables_in_Modules)
The following are of particular interest.
DOSTIM
DOSTIM is the time of a lagged dose or additional dose to which the
system is being advanced. Abbreviated code in $DES may test DOSTIM.
It may use DOSTIM on the right, unless DOSTIM is a random variable.
In this case, it may be used on the right in a $PK block to define a
random variable which may in turn be used on the right in the $DES
block.
DOSREC
DOSREC is the dose record corresponding to the dose entering at DOS-
TIM. Abbreviated code in $AES may test items in DOSREC in a logical
condition, and DOSREC may always be used on the right.
ISFINL
During simulation or a copying pass, and during the advance to a par-
ticular time (event or non-event time), ISFINL=1 at a final call to
DES at that time. Otherwise, ISFINL=0.
DES_DER, MITER, METH
See Diff Eq Solver Settings.
Forbidden Variable Names:
IR DA DP E(n) ETA(n) EPS(n) ERR(n)
PSEUDO ASSIGNMENT STATEMENTS
COMRES=-1
RECORD ORDER:
Follows $SUBROUTINES $INPUT $MODEL $PK
DISPLAYED VALUES
DES-defined variables may be listed for display in $TABLE or $SCATTER. |
The values displayed for the first event record of the data set are |
0's. The values displayed for the first event record of subsequent |
individuals are those from the last event record of the previous indi- |
vidual. This is because there is no call to DES with the first event |
record of the individual record, or with any other event record with |
the same value of TIME. NM-TRAN provides a warning message. |
(WARNING 48) DES-DEFINED ITEMS ARE COMPUTED ONLY WHEN EVENT TIME |
INCREASES. E.G., DISPLAYED VALUES ASSOCIATED WITH THE FIRST EVENT |
RECORD |
OF AN INDIVIDUAL RECORD ARE COMPUTED WITH (THE LAST ADVANCE TO) AN |
EVENT |
TIME OF THE PRIOR INDIVIDUAL RECORD.
The values displayed for event records other than the first are evalu- |
ated at the event time (as are all other displayed items such as PK- |
defined values and data record items).
Note that multiple calls to DES are associated with each event record. |
Some (including the final call during integration) may have a value of |
T that is larger than the end time of the integration interval. When |
NONMEM is performing simulation or a copying pass (COMACT>0), DES |
is called immediately after the advance to an event time or non- |
event time, with a value of T equal to this time, so that displayed |
values are the final value of T. Global variable ISFINL is set by |
PREDPP to 1 on this final call to DES. ISFINL can be tested on a |
WRITE statement if such statements are used in DES.
(See des, advan6, advan8, advan9).
REFERENCES: Guide IV Section V.C.7
REFERENCES: Guide VI Section VI.C
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