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Re: New Pharmacometrics & Systems Pharmacology Journal, Invitation for Applications: Editor-in-Chief

From: Yuhong Chen <chen.yuhong2010>
Date: Mon, 13 Feb 2012 14:23:23 -0500

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

Received on Mon Feb 13 2012 - 14:23:23 EST

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