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 |                        SS DOSE EVENT RECORD                        |
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 MEANING: Specification of steady-state dose for PREDPP
 CONTEXT: $INPUT record and NONMEM data set

 DISCUSSION:
 PREDPP  recognizes two varieties of doses, transient and steady-state.
 Transient doses are described  separately  (See dose_event).   Steady-
 state doses are described here.

 (With  NM75  there  is a new way of computing SS, the Empirical steady
 state method, in which there is no SS data item, and a negative  value
 of ADDL requests the computation.  This is described separately.)
 (See empirical_SS).
 (See Guide Introduction_7)

 A  steady-state  dose  is  a dose that is imagined to be the last of a
 series of implied doses, each exactly like the dose in question, given
 at  a  regular  interval  specified by the II data item and leading to
 steady-state by the time the steady-state dose is given.

 For steady-state doses, the SS data item must be defined and  positive
 (See ss_data_item).

 The  ADDL data item may be used on the SS dose event record to specify
 additional transient doses after the steady-state dose, given  at  the
 interval II.

 The  CMT data item (See cmt) applies to steady-state doses as to tran-
 sient doses.

 PK parameters absorption lag (ALAGn),  bioavailability  (Fn),  modeled
 rates  (Rn)  and modeled durations (Dn) apply to steady-state doses as
 they do to transient doses, except as noted.

 When absorption lag applies, it is understood to apply to all  implied
 doses.   Steady-state  is  computed as if there were no ALAG, and then |
 there is an advance to the appropriate point in the steady-state cycle |
 (II-ALAG).                                                             |
 See Guide VI, Section V.F.4, Note 4                                    |

 MTIME parameters do not apply to steady-state doses.                   |
 See Guide VI, Section V.F.4, Note 3                                    |

 When bioavailability applies, it is understood to apply to all implied
 doses.

 Values of AMT, RATE, II data items:

 AMT   RATE      II

 >0    0         >0   Steady-state with multiple bolus doses.

 >0    >0        >0   Steady-state with multiple infusions.
                      The final infusion is started at the event time of
                      the  SS dose record and continues beyond its event
                      time.  (More than one infusion continues when  the
                      duration  of  the steady-state infusion is greater
                      than II.)

 >0    -1,-2     >0   Steady-state with multiple zero-order bolus doses.
                      The final infusion is started at the event time of
                      the  SS dose record and continues beyond its event
                      time.  (More than one infusion continues when  the
                      duration  of  the steady-state infusion is greater
                      than II.)

 0     0,>0,-1   0    Steady-state with constant infusion.
                      The infusion terminates at the event time  of  the
                      SS dose record.  The ADDL data item cannot be used
                      to specify additional transient doses.  Doses with
                      rate  0 are useful when the differential equations
                      coded by the user explicitly provide  for  endoge-
                      nous drug production.
                      (The  Initial  Steady  State feature (I_SS) may be |
                      specified in the model instead of using a  steady- |
                      state dose record with rate 0.)

REFERENCES: Guide VI Section V.F
REFERENCES: Guide V Section 6.8


  
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