+--------------------------------------------------------------------+
 |                                                                    |
 |                     PK_PD_SEQUENTIAL_1 EXAMPLE                     |
 |                                                                    |
 +--------------------------------------------------------------------+

 This  is  an  example for analysis of direct PD using previously esti-
 mated individuals' PK parameters.  (See PK_PD_sequential_2 example).

 $PROBLEM   EMAX MODEL APPLIED TO EFFECT SITE CONCENTRATION
 ; NOTE: INDIVIDUAL K, V ESTIMATED FROM PREVIOUS PK FIT
 ;       AND RECORDED IN DATA
 ;
 ; THE DATA FILE CONTAINS *ONLY* EFFECT OBSERVATIONS,
 ; CMT = 2  NEEDED TO TELL PREDPP TO SET F = CE
 $DATA   data
 $INPUT  ID TIME DV AMT=DOSE CMT  KK V1
 ;                                |---|
 ;                              KK AND V1 ARE ESTIMATES OF K AND V
 $SUBROUTINES ADVAN3
 $PK
    K  = KK
    K12= .001*K                      ; TRIVIAL LOSS TO EFFECT COMPT.
    K21= THETA(1)*EXP(ETA(1))
    EMAX=THETA(2)*EXP(ETA(2))
    C50= THETA(3)*EXP(ETA(3))
    S2=  V1*K12/K21                  ; SO THAT CESS = CPSS
 $ERROR
    Y  =EMAX*F/(C50+F)*EXP(ERR(1))
 ; ADD APPROPRIATE $THETA, $OMEGA, $SIGMA, $ESTIMATION, ETC.

 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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