PK voie orale, équations différentielles, Michaelis Menten

1 cpt, Elimination Michaelis Menten

$PROB PK 1 cpt voie orale, eq diff, erreur residuelle mixte
$INPUT ID TIME AMT DV EVID CMT
$DATA ..\data.csv IGNORE=#
$SUBROUTINE ADVAN6 TRANS1 TOL=3
$MODEL NCOMP=2
COMP=(DIG, DEFDOSE)
COMP=(CENTRAL, DEFOBS)

$PK
KA = THETA(1) * EXP(ETA(1))
VMAX = THETA(2) * EXP(ETA(2))
V2 = THETA(3) * EXP(ETA(3))
KM = THETA(4) * EXP(ETA(4))
S2 = V2

$DES
CP = A(2)/S2
DADT(1) = -KA*A(1)
DADT(2) = KA*A(1) – VMAX*CP/(KM + CP)

$ERROR
IPRED=F
W=(F*F*THETA(5)**2+THETA(6)**2)**0.5
Y=F+ERR(1)*W
IRES=DV-IPRED
IWRES=IRES/W
$THETA
(0, 2) ; KA ; 1/h
(1, 30, 500) ; VMAX ; Amount/h
(5, 60, 500) ; V2 ; L
(.1) ; KM ; Concentration
(0, .1) ; PROP
(0, 500) ; ADD
$OMEGA
.1 ; ETA_KA
.1 ; ETA_Vmax
.1 ; ETA_V2
.1 ; ETA_KM

$SIGMA
1 FIXED
$EST METHOD=1 INT MAXEVAL=8000 PRINT=5 NOABORT POSTHOC NSIG=3
$COVARIANCE
$TABLE ID TIME DV PRED CMT WRES RES IPRED IWRES IRES FILE=1.fit
$TABLE KA VMX KM V2 FIRSTONLY NOPRINT
FILE=parameter.fit

2 cpt, Elimination Michaelis Menten

$PROB PK 2 cpts voie orale, eq diff, erreur residuelle mixte
$INPUT ID TIME AMT DV EVID CMT
$DATA ..\data.csv IGNORE=#
$SUBROUTINE ADVAN6 TRANS1 TOL=3
$MODEL NCOMP=3
COMP=(DIG, DEFDOSE)
COMP=(CENTRAL, DEFOBS)
COMP=(PERIPH)
$PK
KA = THETA(1) * EXP(ETA(1))
VMAX = THETA(2) * EXP(ETA(2))
V2 = THETA(3) * EXP(ETA(3))
KM = THETA(4) * EXP(ETA(4))
K23 = THETA(5)
K32 = THETA(6)
S2 = V2

$DES
CP = A(2)/S2
DADT(1) = -KA*A(1)
DADT(2) = KA*A(1) -VMAX*CP/(KM + CP) -K23*A(2) +K32*A(3)
DADT(3) = K23*A(2) – K32*A(3)

$ERROR
IPRED=F
W=(F*F*THETA(7)**2+THETA(8)**2)**0.5
Y=F+ERR(1)*W
IRES=DV-IPRED
IWRES=IRES/W
$THETA
(0, 2) ; KA ; 1/h
(1, 30, 500) ; VMAX ; Amount/h
(5, 60, 500) ; V2 ; L
(.1) ; KM ; Concentration
(.1) ; K23 ; 1/h
(.01) ; K32 ; 1/h
(0, .1) ; PROP
(0, 500) ; ADD
$OMEGA
.1 ; ETA_KA
.1 ; ETA_Vmax
.1 ; ETA_V2
.1 ; ETA_KM