+--------------------------------------------------------------------+
| |
| $PK |
| |
+--------------------------------------------------------------------+
MEANING: Marks the beginning of abbreviated code for the PK Routine
CONTEXT: NM-TRAN Control Record
USAGE:
$PK
abbreviated code
DISCUSSION:
The $PK record is used to model the values of basic and additional
pharmacokinetic parameters. It is used with PREDPP.
Basic PK parameters are typically the rate constants ("micro-con-
stants") for use in kinetic formulas. $PK can compute instead parame-
ters such as clearance and volume, and a translator ("TRANS") subrou-
tine can be used to convert these to rate constants. Additional PK
parameters include compartment scale parameters, which PREDPP uses to
convert compartment amounts to concentrations, and dose-related param-
eters such as modeled infusion rates. General rules for abbreviated
code are documented elsewhere
(See abbreviated code).
Specific rules for $PK follow.
ASSIGNMENT AND CONDITIONAL STATEMENTS
Left-hand quantities in assignment statements:
Basic PK parameters for the ADVAN and TRANS routines (Required,
except with the General Nonlinear Kinetics Models ADVAN6, ADVAN8,
ADVAN9, ADVAN13, ADVAN14, ADVAN15, ADVAN16, ADVAN17, ADVAN18). One
or more of the following, depending on which ADVAN and TRANS are
being used.
K CL V (ADVAN1)
KA K CL V (ADVAN2)
K K12 K21 CL V Q VSS V1 V2 ALPHA BETA AOB (ADVAN3)
KA K K23 K32 CL V Q VSS V1 V2 V3 ALPHA BETA AOB (ADVAN4)
Km0 Kmn (ADVAN5, ADVAN7)
P(n) (ADVAN6, ADVAN8, ADVAN9, ADVAN13, ADVAN14, ADVAN15, ADVAN16, ADVAN17, ADVAN18)
VM, KM (ADVAN10)
K K12 K21 K13 K31 CL Q2 Q3 V1 V2 V3 ALPHA BETA GAMMA
(ADVAN11)
KA K K23 K32 K24 K42 CL Q3 Q4 V2 V3 V4 ALPHA BETA GAMMA
(ADVAN12)
P(n) are referred to as "explicit" basic PK parameters.
Any variable defined in $PK may be used on the right-hand side in a
$DES or $AES block; these are "implicit" basic PK parameters.
Additional PK parameters (Optional)
One or more of the following,
depending on the compartments defined for the model.
The digit following the letter is the compartment number.
Scale parameters Sn, e.g.: S1 S2 S3 S4 SC S0.
Bio-availability fractions Fn, e.g.: F1 F2 F3.
Output fractions Fn, e.g.: F2 F3 F4 F0 FO.
Infusion rates Rn, e.g.: R1 R2 R3.
Infusion durations Dn, e.g.: D1 D2 D3.
Absorption lags ALAGn, e.g.: ALAG1 ALAG2 ALAG3.
Time scale: TSCALE (may be written XSCALE).
Model event times MTIME(i), e.g.: MTIME(1) MTIME(2).
(The subscript i is not a compartment number.)
(See MTIME)
Initial compartment amounts (Optional), e.g..: A_0(1) A_0(2).
(See Compartment Initialization Block)
Initial steady state flag I_SS (Optional).
(See advan68, advan9, $model)
(See Initial Steady State: I_SS,ISSMOD).
PK-defined (i.e., PRED-defined) items
Right-hand quantities in assignment statement and in conditions:
Data item labels specified on the $INPUT statement.
THETA(n).
ETA(n) (Used if the data are population.)
PK-defined items that appeared earlier as left-hand
quantities.
NEWIND
Same as the NEWIND argument passed by NONMEM to PREDPP.
NEWIND=0:
First record of the data set.
THETA value may differ from value at last call with this record.
NEWIND=1:
First record of the data set, THETA value does not differ from
value at last call with this record, and PRED is nonrecursive
(see I_REC), or,
First record of a subsequent individual record.
NEWIND=2:
Subsequent data record of an individual record.
ICALL
Same as the ICALL argument passed by NONMEM to PREDPP.
ICALL=1: Initialization.
ICALL=2: Normal call.
ICALL=3: Finalization.
ICALL=4: Simulation.
ICALL=5: Expectation.
ICALL=6: Raw data averages.
Special rules apply to blocks of abbreviated
code that are executed when ICALL is not 2.
(See Initialization-Finalization block, Simulation block).
(See Expectation block, Data_Average block).
Global Variables in Modules
Certain variables in FORTRAN modules can be used.
(See Variables_in_modules)
The following are of particular interest.
DOSTIM DOSREC(n)
If PK is not being called at an additional or lagged dose time, then
DOSTIM = 0 and all elements of DOSREC are 0.
If PK is called at an additional or lagged dose time t, then DOS-
TIM=t
(See Guide VI, Chapter III)
DOSREC contains a copy of the dose event record which initiated the
additional or lagged dose (actually, only of the final row:
EVTREC(NVNT,*)). Data items may be referred to by position or by
label, e.g., DOSREC(1) or DOSREC(ID). In DOSREC, TIME and all user
(concomitant) data items have values from the next event record.
All other NONMEM/PREDPP reserved data items have values from the
initiating dose event record. (The $BIND record may be used to
override this.)
A(n) TSTATE
A(n) are the latest computed compartment amounts, and TSTATE is the
time at which they were computed. That is, A(n) are the amounts at
the previous event time, or if at a later time, but before the time
for which PK is being called, a lagged or additional dose was given,
or a regular infusion was terminated, or a modeled event occurred,
then A(n) are the amounts at the latest such time. If there are
population etas, and A(n) are used in the $PK abbreviated code, then
any $OMEGA records referring to etas explicitly used in this code
should precede the $PK record, or if an $MSFI record is used, it
should precede the $PK record and include the option NPOP=m.
Note: If there is no verbatim code and no explicit use of a sub-
scripted variable A in the $PK record, then the symbol A can be used
as a data item label or as a name of a PK-defined item.
A_0FLG
A_0FLG signals a record with which it is possible to initialize a
compartment amount.
(See Compartment Initialization Block)
Forbidden Variable Names:
IDEF IREV EVTREC NVNT INDXS IRGG GG NETAS DADT(n) E(n) EPS(n)
PSEUDO ASSIGNMENT STATEMENTS
COMRES=-1
CALLFL=-2: Call with every event record and at additional and lagged
dose times.
CALLFL=-1: Call with every event record.
CALLFL=0: Call with first event record and new TIME values.
CALLFL=1: Call once per individual record.
Of the last four, CALLFL=-2 is the default when DOSREC, DOSTIM, or
MTIME are used explicitly in the abbreviated code. Otherwise,
CALLFL=-1 is the default.
The pseudo-assignments statements may be enclosed in parentheses.
If two of them are present in the same set of parentheses, separate
them with a semicolon. A calling protocol phrase may be used within
parentheses instead of a pseudo-assignment statement, and either
upper or lower case may be used. E.g.,
$PK (ONCE PER IR) ; same as CALLFL=1
$PK (NEW TIME) ; same as CALLFL=0
$PK (EVERY EVENT) ; same as CALLFL=-1
$PK (NONEVENT) ; same as CALLFL=-2
RECORD ORDER:
Follows $SUBROUTINES and $INPUT
Follows $MODEL (with General Nonlinear Kinetics Models ADVAN6,
ADVAN8, ADVAN9, ADVAN13, ADVAN14, ADVAN15, ADVAN16, ADVAN17,
ADVAN18).
Precedes $ERROR (if present)
REFERENCES: Guide IV Section V.C.5
REFERENCES: Guide V Section 7
REFERENCES: Guide VI Section III
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