+--------------------------------------------------------------------+
 |                                                                    |
 |                     PK_PD_SEQUENTIAL_2 EXAMPLE                     |
 |                                                                    |
 +--------------------------------------------------------------------+

 This  is  an  example for analysis of direct PD using previously esti-
 mated population PK parameters.  (See PK_PD_sequential_1 example).

 $PROBLEM   EMAX MODEL APPLIED TO EFFECT SITE CONCENTRATION
 ; THE DATA FILE CONTAINS *ONLY* EFFECT OBSERVATIONS,
 ; POP PK PARAMS ESTIMATED IN PREVIOUS RUN & FIXED HERE.
 ; CMT = 2  NEEDED TO TELL PREDPP TO SET F = CE
 ;
 $DATA   data
 $INPUT  ID TIME DV AMT=DOSE CMT
 $SUBROUTINES ADVAN3
 $PK
    K  = THETA(1)*EXP(ETA(1))
    K12= .001*K                      ; TRIVIAL LOSS TO EFFECT COMPT.
    K21= THETA(2)*EXP(ETA(2))
    V1=  THETA(3)*EXP(ETA(3))
    EMAX=THETA(4)*EXP(ETA(4))
    C50= THETA(5)*EXP(ETA(5))
    S2=  V1*K12/K21                 ;  SO THAT CESS = CPSS
 $ERROR
    Y=   EMAX*F/(C50+F)*EXP(ERR(1))
 $THETA
   .124 FIXED                       ; K   - FIXED TO PREV EST
   .1                               ; KEO - ESTIMATED
   28.6 FIXED                       ; V1  - FIXED TO PREV EST
  100                               ; EMAX- ESTIMATED
   50                               ; C50 - ESTIMATED
 $OMEGA
   .113 FIXED                       ; OMEGA(K) - FIXED TO PREV EST
   .04
   .627 FIXED                       ; OMEGA(V1)- FIXED TO PREV EST
   .04
   .04
  $SIGMA .16
 ; ADD $ESTIMATION, ETC, AS DESIRED.

 If, moreover,  an absorption lag (ALAG1) parameter is modeled  in  $PK
 with  parameters estimated from the PD data only, then this introduces
 a lag in the dose - Ce relationship.  Since this lag was  not  present
 in  the  dose - Cp relationship, it may be interpreted as a lag in the
 Cp - Ce relationship.

REFERENCES: Guide IV Section V.C.6
REFERENCES: Guide VI Section IV.B.2, VII.C.3


  
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