群体药动学代码库-nonmem

$PROB RODRIGUES CHILD 2017

$INPUT ID TIME DV AMT II ADDL EVID MDV WT CMT
$DATA 12060000060006001.csv

$SUBROUTINES ADVAN13 TOL=6

$MODEL
COMP(DEPOT,DEFDOS) ; CMT 1
COMP(TRANSI1) ; CMT 2
COMP(TRANSI2) ; CMT 3
COMP(TRANSI3) ; CMT 4
COMP(CENT,DEFOBS) ; CMT 5
COMP(PERI) ; CMT 6
COMP(MHDR) ; CMT 7
COMP(MHDS) ; CMT 8

$PK
; OXC
MTT = THETA(1)EXP(ETA(1))
CLCOX_TOTAL = THETA(2)(WT/68)**0.75EXP(ETA(2))
Q = THETA(3)
VCOXC = THETA(4)(WT/68)EXP(ETA(3))
VPOXC = THETA(5)(WT/68)
FMET = THETA(6)
; MHD
CLMHD = THETA(7)(WT/68)**0.75
FRS = THETA(8)
VMHD_R = THETA(9)(WT/68)EXP(ETA(4))
VMHD_S = THETA(10)(WT/68)*EXP(ETA(5))

$DES
; OXC
KTR = 4/MTT
K5 = CLCOX_TOTAL/VCOXC
K56 = Q/VCOXC
K65 = Q/VPOXC
; MHD
CLM = CLCOX_TOTALFMET
K57 = CLMFRS/VCOXC
K58 = CLM*(1 - FRS)/VCOXC
K70 = CLMHD/VMHD_R
K80 = CLMHD/VMHD_S

DADT(1) = - KTRA(1)
DADT(2) = KTRA(1) - KTRA(2)
DADT(3) = KTRA(2) - KTRA(3)
DADT(4) = KTRA(3) - KTRA(4)
DADT(5) = KTRA(4) - K5A(5) - K56A(5) + K65A(6)
DADT(6) = K56A(5) - K65A(6)
DADT(7) = K57A(5) - K70A(7)
DADT(8) = K58A(5) - K80*A(8)

$ERROR
C_OXC = A(5)/VCOXC
C_MHD_R = A(7)/VMHD_R
C_MHD_S = A(8)/VMHD_S

IPRED=C_OXC ; OXC
IF (CMT.EQ.7) IPRED=C_MHD_R ; R_MHD
IF (CMT.EQ.8) IPRED=C_MHD_S ; S_MHD

Y = IPRED*(1+EPS(1)) ; OXC
IF (CMT.EQ.7) Y = IPRED*(1+EPS(2)) ; R_MHD
IF (CMT.EQ.8) Y = IPRED*(1+EPS(2)) ; S_MHD

IRES=DV-IPRED
DEL = 0
IF (IPRED.EQ.0) DEL=1
IWRES = (1-DEL) * IRES / (IPRED + DEL)

$THETA
; OXC
0.514 ; 1.MTT
84.8 ; 2.CL_COX_total
55.8 ; 3.Q
131 ; 4.Vc_OXC
456 ; 5.Vp_OXC
0.79 ; 6.Fmet
; MHD
2.01 ; 7.CL_MHD
0.19 ; 8.FRS
23.6 ; 9.Vs_MHD
31.7 ; 10.Vr_MHD

$OMEGA
0.02882 ; 1.BSV_MTT
0.03224 ; 2.BSV_CL_OXC
0.05375 ; 3.BSV_Vc_OXC
0.04811 ; 4.BSV_Vr_MHD
0.04811 ; 5.BSV_Vs_MHD

$SIGMA
0.009409 ;1.OXC_EPS
0.000289 ;2.MHD_EPS

$SIMULATION (12345678) ONLYSIM SUBPROBLEM=100
$TABLE ID TIME DV CMT NOAPPEND NOPRINT NOHEADER FILE=s1.fit

参考来源：

[1] Antunes NJ, van Dijkman SC, Lanchote VL, Wichert-Ana L, Coelho EB, Alexandre Junior V, Takayanagui OM, Tozatto E, van Hasselt JGC, Della Pasqua O. Population pharmacokinetics of oxcarbazepine and its metabolite 10-hydroxycarbazepine in healthy subjects. Eur J Pharm Sci. 2017 Nov 15;109S:S116-S123.(https://pubmed.ncbi.nlm.nih.gov/28528287/)