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| DOSE EVENT RECORD |
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MEANING: Specification of dose for PREDPP
CONTEXT: $INPUT record and NONMEM data set
DISCUSSION:
PREDPP recognizes two varieties of doses, transient and steady-state.
Steady-state doses are described separately (See SS_dose_event).
Transient doses are described here.
For a transient dose, the SS data item must be not defined or must be
zero. The ADDL data item may be used to specify additional transient
doses at regular intervals given by II. The dose is introduced into a
dose compartment n, which is defined either explicitly in the event
record (by the value n>0 of the CMT data item), or as the default com-
partment for doses for the particular ADVAN (when the CMT data item is
not defined or contains zero).
Absorption lag applies to the initiating dose and to all subsequent
additional doses. If an absorption lag parameter is defined by PK for
the dose compartment (this parameter is coded ALAGn in abbreviated
code) and has a positive value, then the dose is referred to as a
"lagged dose" and it is actually introduced into the system at a
"lagged time" equal to the time at which the dose would ordinarily be
introduced plus the value of the absorption lag parameter. The value
of ALAGn in effect at time T applies to the dose and to all subsequent
additional doses, even if ALAGn changes value with a subsequent event
record.
Bioavailability applies to the initiating dose and to all subsequent
additional doses. A bioavailability parameter may be defined by PK
for the dose compartment (it is coded Fn in abbreviated code) and must
have a positive value. If no such parameter is defined, the bioavail-
ability parameter is assumed to have the value 1. The value of amount
in the following discussion is the value of the AMT data item multi-
plied by the value of the bioavailability parameter in effect at the
time the dose is actually introduced. Changes in the value of Fn at
later times have no affect on past doses, e.g., infusions and zero-
order bolus doses that are already in progress are unaffected.
The type of dose is described by the values of the AMT and RATE data
items.
AMT RATE
>0 0 Bolus dose.
The dose is introduced into the dose compart-
ment at the event time (before ERROR is
called with the event record).
>0 >0 Infusion dose ("regular infusion").
The infusion is started at the event time.
Its duration is computed as amount/RATE.
>0 -1,-2 Zero-order bolus dose.
Similar to a regular infusion, except that
the duration of a regular infusion is speci-
fied by information in the dose event record
and computed by PREDPP itself, whereas the
duration of a zero-order bolus dose is
regarded as a parameter which may be modeled
and computed by the user's PK routine or $PK
abbreviated code. The infusion is started at
the dose event time.
If RATE=-2, the duration is computed by PK.
The parameter is coded Dn in abbreviated
code, e.g., D1 models the duration of zero-
order bolus doses to compartment 1. The
duration is given by the value of Dn as com-
puted by PK at the dose event time (or lagged
time, if the dose is lagged). Rate is com-
puted as amount/duration and is thus fixed
for this infusion, even if the value of Dn
changes value with a later event record.
If RATE=-1, the infusion rate is computed by
PK. The parameter is coded Rn in abbreviated
code, e.g., R1 models the rate of zero-order
bolus doses to compartment 1. The rate which
applies during the advance from a particular
state time to a later state time is given by
the value of Rn in effect for the the later
time, and may change during the course of the
infusion. The duration at any state time is
computed as amount/rate, where amount repre-
sents the remaining dose amount and rate rep-
resents the value of Rn at the state time.
The infusion continues until the entire dose
amount has been introduced into the system.
CAUTION: If PREDPP is used without using NM-TRAN as a preprocessor |
then any user-supplied negative values for these data items will be |
passed to PREDPP. For a discussion of the circumstances such that the |
data file used by NONMEM and PREDPP is FDATA (in which case NM-TRAN |
has preprocessed it) or is the file named in the $DATA record, see |
NONMEM Users Guide, Part IV.
(See multiple dose example, exogenous supplementation example).
REFERENCES: Guide VI Section III.B.2, V.F, V.G, V.H
REFERENCES: Guide V Section 6.8
REFERENCES: Guide IV Section III.B.5
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