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FinalModel.mod
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;; Author: FWb
$SIZES PD=-400
$PROBLEM PK model for meropenem in critically ill SLEDD patients
$INPUT ID TIME AMT RATE DV EVID DIALID AGE DIUR CLCR KREA ALB HEIGHT WEIGHT SEX BLOFLOW DIALFLOW ULTRFIL BLOVOL MDV OCC CRCLCG TALD
$DATA data_sledd_mero.csv IGNORE=#
$SUBROUTINE ADVAN13 TOL=9
$MODEL COMP (CENT,DEFOBS,DEFDOS)
$PK
IF (OCC.EQ.0) THEN
IOVCL_SLEDD=0
ENDIF
IF (OCC.EQ.1) THEN
IOVCL_SLEDD=ETA(3)
ENDIF
IF (OCC.EQ.2) THEN
IOVCL_SLEDD=ETA(4)
ENDIF
IF (OCC.EQ.3) THEN
IOVCL_SLEDD=ETA(5)
ENDIF
IF (OCC.EQ.4) THEN
IOVCL_SLEDD=ETA(6)
ENDIF
IF (OCC.EQ.5) THEN
IOVCL_SLEDD=ETA(7)
ENDIF
;----------------------------------
CL_RENCLCR = ( 1 + THETA(6)*(CLCR - 4.13))
CL_RENCOV=CL_RENCLCR
;----------------------------------
IF (DIALID.EQ.1) THEN
TVCL_SLEDD = THETA(5)
CL_SLEDD = TVCL_SLEDD * EXP(IOVCL_SLEDD) ; assuming log-normal distribution of individual PK parameters and normal distribution of IOV
ELSE
TVCL_SLEDD = 0
CL_SLEDD = TVCL_SLEDD
ENDIF
;----------------------------------
TVCL_REN = THETA(1)
TVCL_REN = CL_RENCOV*TVCL_REN
CL_REN = TVCL_REN *((WEIGHT/70)**0.75) * EXP(ETA(1)) ; assuming log-normal distribution of individual PK parameters and normal distribution of IIV
CL = CL_SLEDD + CL_REN
TVV = THETA(2)
V = TVV *(WEIGHT/70) * EXP(ETA(2))
K10 = CL/V
KA = RATE
S1 = V
$DES
DADT(1)= - K10 * A(1)
$THETA
(0,2.99534,10) ;CL_REN
(0,36.756,100) ;V
0 FIX ;additive error
(0,0.391525,5) ;proportional error
(0,2.63404,20) ;CL_SLEDD
$THETA (-0.012,0.0268148,0.242) ;CL_REN_CLCR
$OMEGA
0.04862 ;IIV_CL_REN
0 FIX ;IIV_V
$OMEGA BLOCK (1) 0.1 ;IOV CL_SLEDD_OCC1
$OMEGA BLOCK (1) SAME ;IOV CL_SLEDD_OCC2
$OMEGA BLOCK (1) SAME ;IOV CL_SLEDD_OCC3
$OMEGA BLOCK (1) SAME ;IOV CL_SLEDD_OCC4
$OMEGA BLOCK (1) SAME ;IOV CL_SLEDD_OCC5
$SIGMA
1 FIX ; EPS(1)
$ERROR
MERO= A(1)/S1
IPRED=MERO
W=SQRT(THETA(3)**2+(THETA(4)*IPRED)**2)
DEL=0
IRES=DV-IPRED
IWRES=IRES/W
Y=IPRED + W* EPS(1)
IF(IPRED.EQ.0) DEL=0.0001
$ESTIMATION METHOD=1 INTERACTION MAXEVAL=9999 SIG=2 PRINT=5 NOABORT
MCETA=1
$COVARIANCE PRINT=E
$TABLE ID TIME TALD DIALID OCC CL_REN CL_SLEDD ETA1 ETA2 ETA3 ETA4 ETA5 ETA6 ETA7 CLCR CL DV MDV EVID PRED IPRED RES IRES WRES KREA ALB HEIGHT WEIGHT SEX BLOFLOW DIALFLOW ULTRFIL BLOVOL CRCLCG TALD IWRES CWRES NOAPPEND ONEHEADER NOPRINT FILE=sdtab
$TABLE ID TIME TALD CL_REN CL_SLEDD DV MDV EVID PRED IPRED RES CWRES IRES WRES IWRES CL V ETA1 ETA2 ETA3 ETA4 ETA5 ETA6 ETA7 DIALID AGE DIUR CLCR CRRT KREA ALB HEIGHT WEIGHT SEX BLOFLOW DIALFLOW ULTRFIL BLOVOL CRCLCG TALD FIRSTONLY ONEHEADER NOPRINT FILE=patab