NONLINEAR PK MODEL ERROR
Dear nmusers,
I have a compound with nonlinear CL. I tried to run the nonlinear model but
got error message as following, could someone point out what could be the
error in my control file or my data?
Best regards,
Yuhong
0PROGRAM TERMINATED BY OBJ
ERROR IN CELS WITH INDIVIDUAL 1 ID= 1.00000000000000E+00
SUM OF "SQUARED" WEIGHTED INDIVIDUAL RESIDUALS IS INFINITE
MESSAGE ISSUED FROM ESTIMATION STEP
AT INITIAL OBJ. FUNCTION EVALUATION
My control file is
$INPUT ID STUD STYP DOSE AMT EVID MDV TIME DV HEIG WT BMI AGE SEX RACE
$DATA ../data/M_PK.NM.csv IGNORE=#
$SUBROUTINE ADVAN6 TRANS1 TOL=3
$MODEL NCOMP=3
COMP=(DEPOT DEFDOSE)
COMP=(CENT DEFOBS)
COMP=(PERIPH)
$PK
ALAG1 = THETA(1)
KA = THETA(2)
V2 = THETA(3)
Q = THETA(4)
V3 = THETA(5)
TVM = THETA(6)
KM = THETA(7)
;####################################################################
; Define IIV parameters
;ZLAG = ETA(1)
;ZKA = ETA(2)
;ZV2 = ETA(3)
;ZQ3 = ETA(4)
;ZV3 = ETA(5)
ZVM = ETA(1)
;ZKM = ETA(3)
;########################################################################
; NONMEM PK Parameter Definitions
VM = TVM*EXP(ZVM)
;KM = TKM*EXP(ZKM)
;V2 = TV2*EXP(ZV2)
;Q = TQ3*EXP(ZQ3)
;V3 = TV3*EXP(ZV3)
;KA = TKA*EXP(ZKA)
;ALAG1 = TLAG*EXP(ZLAG)
S2 = V2/1000
;###########################################################################
$DES
; PK Model
CP = A(2)/S2
DADT(1) = - KA*A(1)
DADT(2) = KA*A(1) - Q/V2*A(2) + Q/V3*A(3) - CP*VM/(KM+CP)
DADT(3) = Q/V2*A(2) - Q/V3*A(3)
;###########################################################################
$ERROR
Y = F + F*EPS(1)+EPS(2)
IPRE = F
;##########################################################################
; SECONDARY PARAMETERS
;##########################################################################
$THETA
(0,1) ; ALAG1 [hr]
(0,4) ; KA [1/hr]
(0,4) ; V2 [L]
(0,0.1) ; Q3 [L/hr]
(0,10) ; V3 [L]
(0,100) ; VM [ng/mL/hr]
(0,10) ; KM [ng/mL]
$OMEGA
;0.5 ; ZLAG
;0 FIX ; ZKA
;0 FIX ; ZV2
;0 FIX ; ZQ3
;0 FIX ; ZV3
0.5 ; ZVM
;0.5 ; ZKM
$SIGMA
0.02 ; Proportional
0 FIX ; Additive [ug/mL]
$EST PRINT=20 MAXEVAL=9999 POSTHOC NOABORT METHOD=1 POSTHOC INTER
MSF=MSFO.msf
$COV MATRIX=S PRINT=E
$TABLE ID TIME IPRE EVID MDV AMT DV ALAG1 VM KM V2 V3 Q KA ZVM
STUD DOSE AGE WT BMI SEX RACE NOPRINT ONEHEADER FILE=nmout.tab