PharmPK Discussion - PKPD model setup

• On 4 Nov 2011 at 11:26:10, John Lee (john070170.-at-.yahoo.com) sent the message
  

  
  Dear All,
  
  I am trying to do a PKPD modeling after a single dose of drug using the
  following code, however, the model cannot go through. Part of dataset is
  listed below, does anyone can give me some suggestions?
  
  Thanks
  John
  
  $INPUT
  C ID TIME CP DV MDV
  
  $PRED
  
    E0  =THETA(1)             ; Baseline
    EMAX=THETA(2)             ; Max Effect
    CE50=THETA(3)             ; CE50,
    KE0 =THETA(4)*EXP(ETA(1)) ; Ke0
  
    IF (TIME.EQ.0) THEN
      CE    = 0               ; Conc at effect site
      PTIME = 0               ; Prior Time
      PCP   = 0               ; Prior plasma concentration
      PCE   = 0               ; Prior effect site concentration
    ENDIF
  
    DT=TIME-PTIME
  
    IF (DT.EQ.0) THEN
      DT1=1
    ELSE
      DT1=DT
    ENDIF
  
    IF(CP.GT.PCP) THEN
      SLOPE = (CP-PCP)/DT1
      DELTA = DT1*SLOPE+(KE0*PCP-SLOPE)*(1-EXP(-KE0*DT1))/KE0
    ELSE
      SLOPE = (LOG(CP)-LOG(PCP))/DT1
      DELTA = PCP*KE0/(KE0+SLOPE)*(EXP(DT1*SLOPE)-EXP(-KE0*DT1))
    ENDIF
  
    IF (DT.GT.0) THEN
      CE = PCE*EXP(-KE0*DT)+DELTA
    ELSE
      CE = PCE
    ENDIF
  
    ; Emax PD model with simple additive error
       E = E0 + EMAX*CE/(CE + CE50) ;+ EPS(1)
  
    ; Variables for NONMEM to remember at the next iteration
      PTIME = TIME  ; Prior Time
      PCP = CP      ; Prior plasma concentration
      PCE = CE      ; Prior effect site concentration
  
     DEL = 0
     IF (E.EQ.0) DEL = 1
  
     IPRE = E                     ; INDIVIDUAL PREDICTION
     IRES = DV - IPRE             ; INDIVIDUAL RESIDUAL
     IWRE = IRES / (IPRE + DEL)   ; INDIVIDUAL WEIGHTED RESIDUAL
  
     Y = E * (1 + EPS(1))         ; ERROR EPS (PROPORTIONAL)
  
  $THETA
    (0.5, 7, 20)   ; E0
    (1, 90, 100)  ; EMAX
    (0.5, 3, 50)  ; EC50
    (0.1, 1, 50)  ; KE0
  
  $OMEGA
  
    0 FIX  ;0.05        ; [E] BETWEEN SUBJECT VARIABILITY (KE0)
  
  $SIGMA
  
     0.02         ; [P] WITHIN SUBJECT VARIABILITY
  
  $COV MATRIX=S PRINT=E
  
  $EST MAXEVAL=9990 METHOD=CONDITIONAL
       SIGDIGITS=3 PRINT=10 NOABORT MSF=001.MSF
  
  $TABLE
         ID TIME CP CE E0 EMAX CE50 KE0 MDV
         ETA1 PRED IPRE IRES IWRE
         NOPRINT ONEHEADER FILE=001
  
  C  ID  TIME  CP  DV  MDV
  ..  1  0  0  7.84  0
  ..  1  0.5  57.232  34.3  0
  ..  1  1  73.5  62.72  0
  ..  1  1.5  75.754  76.44  0
  ..  1  2  60.662  85.26  0
  ..  1  2.5  50.176  85.26  0
  ..  1  3  33.222  95.06  0
  ..  1  3.5  40.376  50.96  0
  ..  1  4  20.874  32.34  0
  ..  1  5  7.399  14.7  0
  ..  1  6  1.9306  9.8  0
  ..  1  7  0.7007  11.76  0
  ..  1  8  0.3969  7.84  0
  ..  2  0  0  6.86  0
  ..  2  0.5  39.69  26.46  0
  ..  2  1  28.42  47.04  0
  ..  2  1.5  26.46  51.94  0
  ..  2  2  13.916  32.34  0
  ..  2  2.5  7.4382  23.52  0
  ..  2  3  5.0666  31.36  0
  ..  2  3.5  2.4402  46.06  0
  ..  2  4  0.97412  20.58  0
  C  2  5  .  .  1
  C  2  6  .  .  1
  C  2  7  .  .  1
  C  2  8  .  .  1
  ..  3  0  0  6.86  0
  ..  3  0.5  35.28  77.42  0
  C  3  1  .  .  1
  ..  3  1.5  38.612  92.12  0
  ..  3  2  30.086  87.22  0
  ..  3  2.5  19.502  75.46  0
  ..  3  3  14.994  75.46  0
  ..  3  3.5  7.056  52.92  0
  ..  3  4  1.5582  41.16  0
  ..  3  5  0.43512  24.5  0
  ..  3  6  0.24892  16.66  0
  C  3  7  .  .  1
  C  3  8  .  .  1
  
  

  Back to the Top

Copyright 1995-2011 David W. A. Bourne (david@boomer.org)