$MODEL
Specifies the MODEL subroutine of PREDPP.
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Discussion
Required with a general ADVAN (ADVAN5,6,7,8,9,13,14,15,16,17,18). It is only required for the first problem specification. It applies for all problem specifications in the control stream, and it must not appear with a problem specification other than the first.
Options
NCOMPARTMENTS=n1
The total number of compartments other than the output compartment.
Default: the number of COMPARTMENT options. May also be coded NCM
or NCOMPS. The maximum valee is given by constant PC in
resource/SIZES.f90; With NONMEM 7, the default is 30. (The value may
be over-ridden by user via $SIZES record up to a maximum of 999).
NEQUILIBRIUM=n2
Number of equilibrium compartments, n2 must be less than or equal to n1. If omitted, n2 is computed from the attributes of the COMPARTMENT clauses. If given, the last n2 compartments are understood to be equilibrium compartments, whether or not any of these compartments are defined with COMPARTMENT clauses which include the EQUILIBRIUM attribute.
NPARAMETERS=n3
Number of basic PK parameters. Default: The number of basic PK
parameters defined in the $PK abbreviated code. May also be
coded NPARAMS. May be 0 with the general non-linear models
(ADVAN6, ADVAN8, ADVAN9, ADVAN13, ADVAN14, ADVAN15, ADVAN16,
ADVAN17, ADVAN18). When omiited or general linear model is used, the
number of basic PK parameters is the total number of K-type parameters
recognized in the abbreviated code. In the case of a general nonlinear
model and TRANS1, the number of basic parameters is the the largest
index used with the P array in PK code, or the number of variables
defined in PK abbreviated code and used in DES and/or AES abbreviated
codes, whichever is greater.
COMPARTMENT
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Each COMPARTMENT option defines a single compartment. Compartments are numbered in the order in which they are defined. The name option gives the name for the compartment. The name option may not be one of the compartment attributes below, unless it is enclosed in quotes (' or "). If the name option is not used, then the compartment is named "COMPn," where n is the compartment number.
Attributes are chosen from the following list. When not given, its opposite is the default.
- INITIALOFF: Compartment is initially off.
- NOOFF: Compartment may not be turned on or off.
- NODOSE: Compartment may not receive a dose.
- EQUILIBRIUM: Compartment is an equilibrium compartment (ADVAN9, ADVAN15, and ADVAN17 only; implies NODOSE).
- EXCLUDE: Compartment amount is excluded from the computation of the amount (Amt) of the output compartment (ADVAN9, ADVAN15, and ADVAN17 only). [Amt=(total amount of drug thus far input into system) minus (total amount remaining in the system)]
The following two attributes have no opposites.
- DEFOBSERVATION: Compartment is the default observation compartment. If omitted, the first compartment defined with the name "CENTRAL" is the default observation compartment. If no "CENTRAL" compartment named, the first compartment is the default observation compartment.
- DEFDOSE: Compartment is the default dose compartment. If omiited, the default is the first compartment with the name DEPOT which may receive doses; otherwise, the first compartment which may receive doses.
The attributes INITIALOFF NODOSE define an output-type compartment. As with the output compartment, it is possible to use a negative value of CMT to obtain an observation and turn off such a compartment with one observation record. Like the output compartment, it is initially off, and it remains off (so that the amount therein remains zero) until it is explicitly turned on by an other type event record which has the output compartment's number in the CMT data item. Unlike the output compartment, a differential equation (DADT) must be supplied for an output-type compartment.
LINK compname [TO|AND] compname BY k [l]
Link clauses are used with ADVAN5/ADVAN7 and when the PK routine is user-supplied LINK defines a route of first-order drug distribution between two compartments A & B that are specified in the COMPARTMENT clause (a compartment number can also be used).
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indicates the distribution occurs from A to B, with rate constant "k".1 (It is the number of the row of the GG array where, as a result of basic parameter translation by the TRANS routine, the typical/subject-specific value and ETA derivatives for k can be located; see Guide VI, section III.M.)
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indicates a two-way distribution with rate constant k (A to B) and l (B to A).
I_SS
I_SS may be used with the general non-linear models (ADVAN6, ADVAN8, ADVAN9, ADVAN13, ADVAN14, ADVAN15 ) to request the initial state feature of PREDPP. Values of n are
- I_SS=0: No initial state state (the default)
- I_SS=1: Initial steady state
- I_SS=2: Initial steady state, adds to current compartment amounts.
- I_SS=3: Initial steady state, use current compartment amounts as initial estimates.
The results are identical to those that would be computed by a steady-state dose event record with SS=I_SS and AMT=0 and RATE=0. If endogenous drug is specified in the differential equations, non-zero initial conditions will be computed.
Record order
Follows $SUBROUTINES
Precedes $PK (if present)
Symbolic label substitution (NM75)
Compartment names defined in $MODEL are automatically available for
substitution in abbreviated code. This is referred to as "implicit"
compartment name substitution. It is an alternative to "explicit"
compartmet name substitution using $ABBR REPLACE records
For example:
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allows susbsitutions to be made for A(GUT), DADT(GUT), A(CENTRAL), DADT(CENTRAL), etc, so you may use these symbols in your abbreviated code, as in the following:
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In the generated code, compartment names are replaced by the appropriate values 1, 2, etc.
K is an alias for LINK. In addition, "BY" may be coded "IS", or =, or omitted. Thus "Kmn=k" is equivalent to "LINK m TO n BY k". When the number of compartments exceeds 10, the LINK clause syntax "Kmn=k" may be ambiguous. The letter T may be used to separate the two compartment numbers KmTn.