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run140.mod
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run140.mod
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;; 1. Based on: run139
;; 2. Description: IG, Three dose, CL, BIO, CL adjust by dose
;; x1. Author: RZ
$PROBLEM METABOLISM OF ARCTIGENIN IN RATS AFTER IV - ADVAN6
$DATA Arctigenin_IG_for_nonmem.csv IGNORE=@
$INPUT ID TIME DV DOSE=AMT MDV CMT DL
$SUBROUTINE ADVAN6 TOL=6
$MODEL
COMP=(LUMEN DEFDOSE) ; 1. intestine lumen
COMP=(AG_CENTR) ; 2. AG in central
COMP=(AA_CENTR) ; 3. AA in Central
COMP=(AR_INTES) ; 4. AR in Intestine compartment
COMP=(AG_INTES) ; 5. AG in intestine
COMP=(AA_INTES) ; 6. AA in intestine
$PK
Ka = THETA(1)*EXP(ETA(1)) ; absorption rate of AR
K20= THETA(2)*EXP(ETA(2)) ; elimination rate of AG from Central
K30= THETA(3)*EXP(ETA(3)) ; elimination rate of AA from central comp
V2= THETA(4) ; volume of central
S2= V2
S3= V2
CLI= THETA(5)*EXP(ETA(4)) ; Clearance of intestine
CLB= THETA(6)*EXP(ETA(5)) ; Clearance of Blood
F1= THETA(7)*EXP(ETA(6)) ; Bioavailability
Ki=CLI/V2
Kb=CLB/V2
;K52= THETA(8)
;K63= THETA(9)
;K63= THETA(10)
;K36= THETA(11)
$DES
IF(DL==1)THEN
tKi=Ki*1.314277
ENDIF
IF(DL==3) THEN
tKi=Ki*0.610052
ENDIF
IF(DL==2)THEN
tKi=Ki
ENDIF
DADT(1)=-Ka*A(1)
DADT(2)= tKi*A(5)-K20*A(2)
DADT(3)= Kb*A(6)-K30*A(3)
DADT(4)= Ka*A(1)-tKi*A(4)-Kb*A(4)
DADT(5)= tKi*A(4)-tKi*A(5)
DADT(6)= Kb*A(4)-Kb*A(6)
$ERROR
IPRED = F
;W =SQRT(THETA(8)**2*IPRED**2 + THETA(9)**2)
W =1
Y = IPRED + W*EPS(1)
IRES = DV-IPRED
IWRES = IRES/W
$THETA
(0, 40) ; Ka
(0, 0.4) ; K20
(0, 0.8) ; K30
(0, 0.7) ; V2(L)
(0, 15) ; CLI
(0, 10) ; CLB
(0,0.01,1) ; BIO
;(0, 0.1) ; Prop.RE (sd)
;(0, 0.1) ; Add.RE (sd)
;(0, 9) ; K52
;(0, 9) ; K25
;(0, 9) ; K63
;(0, 9) ; K36
$OMEGA
0 FIX ; IIV Ka
0 FIX ; IIV K20
0 FIX ; IIV K30
0 FIX ; IIV CLI
0 FIX ; IIV CLB
0 FIX ; IIV BIO
$SIGMA
0.000432 ; Residual error
$EST METHOD=0 MAXEVAL=999 NOABORT SIG=5 PRINT=1
$COV
; Xpose
$TABLE ID TIME DV MDV CMT DL ONEHEADER NOPRINT FILE=sdtab140.tab
$TABLE ID Ka K20 K30 V2 ONEHEADER NOPRINT FILE=patab140.tab