+--------------------------------------------------------------------+
 |                                                                    |
 |                           RATE PARAMETER                           |
 |                                                                    |
 +--------------------------------------------------------------------+

 MEANING: Rate (R) parameter for PREDPP
 CONTEXT: Additional PK Parameters

 USAGE:
 $PK
  R1= ....

 DISCUSSION:

 Rate parameters are used with PREDPP.  They are optional additional PK
 parameters.  With NM-TRAN, they are symbolized in  the  $PK  block  by
 reserved  variables Rn, where n is the compartment number to which the
 parameter applies.

 There is one rate parameter associated with every possible  dose  com-
 partment  of the kinetic model (the output compartment is not a possi-
 ble dose compartment) and the rate parameter used for a given dose  is
 that  one associated with the compartment into which the dose is given
 (the dose compartment).

 A rate-modeled zero-order bolus dose is actually an infusion, but  one
 whose rate is given by the rate parameter computed by the PK routine.

 Rate parameters are optional in the sense that rate parameters associ-
 ated with compartments never receiving rate-modeled  zero-order  bolus
 doses or rate-modeled steady-state infusions may be ignored.  However,
 if the RATE data item on some dose event record contains the value -1,
 then a rate parameter for the dose compartment must be computed in the
 PK routine.

 Rate parameters act continuously. PREDPP obtains the value of  a  rate
 parameter, holding over the state-interval ( t1 , t2 ), from a call to
 PK with the record associated with t2, even if  the  dose  event  time
 occurs before t2.  Therefore, if there are state times (e.g. t2) fall-
 ing within the time  interval  over  which  a  zero-order  bolus  dose
 appears  in  the system, there exists the possibility that the rate of
 drug input can change during the interval. For this to occur, the rate
 parameter  would  need  to be modeled in terms of time varying covari-
 ates.  As a result, a zero-order bolus dose where the rate is  modeled
 might be better described as a piecewise zero-order process.

 When  additional  doses  are specified on a dose event record the rate
 parameter applies to the dose and to all the additional doses.

 (See cmt, rate, pk, $pk, default_compartment).
 (See exogenous supplementation example).

REFERENCES: Guide IV Section V.C.5
REFERENCES: Guide V Section 12.2.3
REFERENCES: Guide VI Section III.F.4-5


  
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