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| PK |
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MEANING: PK subroutine
CONTEXT: User-supplied subroutine; for use with PREDPP
USAGE:
SUBROUTINE PK (ICALL,IDEF,THETA,IREV,EVTREC,NVNT,INDXS,IRGG,GG,NETAS)
INTEGER ICALL,IDEF,IREV,INDXS,IRGG,NVNT
DIMENSION IDEF(7,*),THETA(*),EVTREC(IREV,*),INDXS(*),GG(IRGG,LVR+1,*)
(If double precision is to be used):
DOUBLE PRECISION THETA,GG
(If single precision is to be used):
REAL THETA,GG
The value of LVR must be the same as that found in file SIZES
(See sizes).
DISCUSSION:
The PK subroutine is called by PREDPP to obtain values for basic and
additional pharmacokinetic parameters. Basic PK parameters are typi-
cally the rate constants ("micro-constants") for use in kinetic formu-
las. PK can compute instead parameters such as clearance and volume,
and a translator ("TRANS") subroutine can be used to convert these to
rate constants. Additional PK parameters include compartment scale
parameters, which PREDPP uses to convert compartment amounts to con-
centrations, and dose-related parameters such as modeled infusion
rates.
Input argument:
ICALL
ICALL=1: PK has been called for initialization at the beginning
of a NONMEM problem; one such call per problem. EVTREC contains
the first event record. THETA contains the initial estimates.
PK must return values in IDEF, which inform PREDPP what tasks it
will perform at later calls. It may also set GG (k,1,1) to 1,
indicating that the kth PK parameter will be modeled as a log (a
feature which cannot be specified using abbreviated code).
ICALL=2: PK has been called to obtain parameter values; multiple
calls occur. PK should call GETETA to obtain ETA values for the
individual. PK should compute all relevant portions of GG.
ICALL=4: PK has been called during the Simulation Step; multiple
calls occur. PK should call SIMETA to obtain simulated ETA
values for the individual. PK should compute individual-specific
parameters for column 1 of GG.
ICALL=5: PK has been called during the computation of expecta-
tions; multiple calls occur. Such calls occurs when the marginal
(MRG_) data item is defined in the data set and has non-zero
values for some records. If the MRG_ data item has the value 1
or 2, the values of PK-defined items contribute to the expecta-
tions computed for these items.
THETA
The NONMEM THETA vector.
EVTREC
The PREDPP event record.
INDXS
The values specified in the $INDEX record of the NM-TRAN control
stream. (This is the NONMEM Index array starting at position 12,
the first position beyond those positions used by PREDPP itself).
NETAS
The number of population etas in the problem.
Output argument:
IDEF
PK should store values in IDEF only when ICALL=1.
Values may be stored in the following elements:
IDEF(1,1)=-9 (required)
IDEF(1,2) is the call limiting element (compare $PK's CALLFL).
Values are:
-2: call with every event record and at additional and lagged
dose times.
-1: call with every event record (default)
0: call with first event record and new TIME values
1: call once per individual record
Compartment initialization may be performed by routine PK;
(See PRDPK3, PROCMC).
An initial steady state may be requested by routine PK; |
(See PRDPK4, i_ss, initial_condition). |
The value in IDEF(1,3) describes whether PK performs compartment
initialization, i.e., whether or not PK initializes elements of
the initial state vector A_0(n). Values are:
-1: PK may initialize A_0.
0: PK does not initialize A_0.
1: PK does initialize A_0.
The default used by PREDPP is IDEF(1,3)=-1. However, when com-
partment initialization is not implemented, then if IDEF(1,3) is
set to 0, PREDPP can avoid some time-consuming processing.
Indeed, when $PK abbreviated or verbatim code is supplied, and
there is no reference to compartment initialization amounts
A_0(n) in either the abbreviated or verbatim code, then NM-TRAN
sets IDEF(1,3)=0.
Compartment amounts may be used by routine PK; (See PROCM4). The
value in IDEF(1,4) describes whether PK uses derivatives of com-
partment amounts (e.g. compartment amounts themselves are used as
random variables in arithmetic statements in PK). Values are:
-1: PK may use derivatives of compartment amounts.
0: PK does not use derivatives of compartment amounts.
1: PK uses derivatives of compartment amounts.
The default used by PREDPP is IDEF(1,4)=-1. However, when deriva-
tives of compartment amounts are not used, then if IDEF(1,4) is
set to 0, PREDPP can avoid some time-consuming processing.
Indeed, when $PK abbreviated or verbatim code is supplied, and
there is no reference to A(n) (as a random variable in an arith-
metic statement) in the abbreviated code (or to derivatives of
A(n) in the verbatim code), then NM-TRAN sets IDEF(1,4)=0.
Remaining elements contain row numbers in GG:
IDEF(2,1): row number of F0 (output fraction)
IDEF(2,2): row number of XSCALE (Time Scale)
IDEF(3,n): row number of Sn (Scale for comp. n)
IDEF(4,n): row number of Fn (bioavailability fraction for comp. n)
IDEF(5,n): row number of Rn (modeled rate for comp. n)
IDEF(6,n): row number of Dn (modeled duration for comp. n)
IDEF(7,n): row number of ALAGn (absorption lag for comp. n)
GG The array of PK parameters and their eta derivatives. The max-
imum number of rows in GG is given by IRGG, which is the same as
constant PG found in file SIZES (See sizes).
At ICALL = 2:
GG(k,1,1) contains the value of the kth parameter.
GG(k,i+1,1) contains its derivative with respect to the ith eta.
GG(k,i+1,j+1) contains its second derivative with respect to the
ith eta and the jth eta (lower-triangular; j=1, ..., i). (Second
derivatives are only needed with estimation by the Laplacian
method.)
At ICALL = 4:
GG(k,1,1) contains the individual-specific value of the kth
parameter. Other columns of GG need not be computed.
Also see NONMEM read-only commons (of the form ROCMn), NONMEM-PRED
commons (of the form NMPRDn), and PREDPP read-only commons (of the
form PROCMn).
REFERENCES: Guide IV Section V.C.5
REFERENCES: Guide V Section 7
REFERENCES: Guide VI Section III
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