;; 1. Based on: run03
;; 2. Description: EST DOCETAXEL_HUMAN Run=3
;; x1. Author: user
$SIZES LIM6=2000
$PROBLEM DOCETAXEL_HUMAN Run=3
;Kineticist Sonya Tate
;Docetaxel: AUC-driven model
$INPUT CCOM,ID,TIME,DV,AMT,CMT,EVID,MDV,DOSE1,AUC1,DOSE2,AUC2,AUC2M,DOSE3,AUC3

$DATA EST_S273_S188_TUMOUR_AUC.csv IGNORE=C
$SUBROUTINE ADVAN6 TOL=3

;Notes: CLARET ET AL 2009 MODEL
;Notes: ABSOLUTE TUMOUR SIZE
;plot diagnostic (PRED,IPRED,CPRED,CPREDI,EPRED)
;plot individual x=(TIME) y=(DV,IPRED,PRED)

$MODEL
;Tumour
COMP=(TUMOUR)

$PK
;Tumour
BASE   = THETA(1)*EXP(ETA(1))
KG     = THETA(2)*EXP(ETA(2))
KD     = THETA(3)*EXP(ETA(3))
LAMBDA = THETA(4)*EXP(ETA(4))

A_0(1)=BASE

$ERROR
IPRED=F
W=F+0.0001
IRES=DV-IPRED
IWRES=IRES/W
Y=F+ERR(1)

$DES
;Tumour
DOC = AUC1
DADT(1) = KG*A(1) - KD*EXP(-LAMBDA*T)*DOC*A(1)

$THETA (0,5)           ;BASE
$THETA (0,0.0001)      ;KG
$THETA (0,0.000001)    ;KD
$THETA (0,0.001)       ;LAMBDA

$OMEGA 0.1             ;BASE
$OMEGA 0.1             ;KG
$OMEGA 0.1             ;KD
$OMEGA 0.1             ;LAMBDA

;Residual error
$SIGMA 1               ;ADD

$EST MAXEVAL=9000 PRINT=5 METH=1 INTER

$COV

$TABLE ID TIME DV IPRED IWRES CPRED CWRES CPREDI CWRESI EPRED EWRES BASE KG KD LAMBDA DOSE1 AUC1 DOSE2 AUC2 AUC2M DOSE3 AUC3

FILE=sdtab04 NOPRINT ONEHEADER