Please see my comments inserted below about the values of IPRED,W, etc.
for each type of error model
I hope the modeling goes well.
Luann
On 8/24/2015 9:16 PM, Chiaying Lin wrote:
Dear NM-Users,
I'm a NONMEM beginner. The following are my control stream for a
monoclonal antibody which clears via target mediated disposition.
However, when I ran NONMEM, I didn't get minimization successful
message (in fact, no message at all), there are also no Table output
and the xx.g77 file contains only empty three output files. I will be
appriciated if someone help to find mistakes. Thanks.
Peggy
---------------------------------------------------------------------------------------------------------------------------------------
$PROBLEM **base model**
$DATA PKDATA.CSV IGNORE=C
$INPUT ID TIME AMT NDV=DROP LNDV=DV EVID MDV CMT BW AGE DOSE
$SUBROUTINE ADVAN6 TRANS1 TOL=3
$MODEL NCOMP=2 NPAR=6
;COMP=(CENTRAL DEFOBSERVATION DEFDOSE)
;COMP=(PERIPH)
$PK
TVVMAX=THETA(1)
VMAX=TVVMAX*EXP(ETA(1))
KM=THETA(2)
TVV1=THETA(3)
V1=TVV1*EXP(ETA(2))
TVV2=THETA(4)
V2=TVV2*EXP(ETA(3))
Q=THETA(5)*EXP(ETA(4))
S1=V1
$DES
C1=A(1)/V1
C2=A(2)/V2
DADT(1)=-VMAX*C1/(KM+C1)-(Q*C1)+(Q*C2)
DADT(2)=(Q*C1)-(Q*C2)
$ERROR
CALLFL=0
IPRED=LOG(F)
IRES=DV-IPRED
IWRES=IRES/IPRED
For CCV error model
IPRED=F
W=IPRED
Y=IPRED+W*ERR(1)
For LOG error model
IPRED=LOG(F)
W=1
Y=IPRED+W*ERR(1)
For additive error model
IPRED=F
W=1
Y=IPRED+W*ERR(1)
For additive + CCV error model
IPRED=F
W=SQRT(IPRED**2*SIGMA(1,1) + SIGMA(2,2))
Y=F + F*EPS(1)+EPS(2)
The following is true for all of the above models
IRES=DV-IPRED
IWRES=IRES/W
Y=IPRED+ERR(1)
$THETA
(0.1, 1.49, 5) ;VMAX (mg/hr)
(1, 50,300) ;KM (μg/mL)
(1.3, 2.72, 5) ;V1 (L)
(1.1, 2.43, 5) ;V2 (L)
(0.001, 0.095, 1) ;Q (L/hr)
$OMEGA .025 ;VMAX
$OMEGA .032 ;V1
$OMEGA .29 ;V2
$OMEGA .975 ;Q
$SIGMA
0.030 ;ERR(1)
$ESTIMATION METH=1 MAXEVAL=9999 PRINT=5 POSTHOC
$COVARIANCE
$TABLE ID TIME DV IPRED IWRES VMAX KM V1 V2 Q ETA1 ETA2 ETA3 ETA4 BW
AGE NOPRINT ONEHEADER FILE=1.fit
$TABLE ID TIME AMT IPRED IWRES NOPRINT ONEHEADER FILE=sdtab1
$TABLE ID VMAX KM V1 V2 Q ETA1 ETA2 ETA3 ETA4 NOPRINT ONEHEADER
FILE=patab1
$TABLE ID BW AGE NOPRINT ONEHEADER FILE=cotab1
----------------------------------------------------------------------------------------------------------------------------------
#ID TIME AMT
NDV
LNDV
EVID MDV CMT BW AGE DOSE
A-P001 0 81.3 . . 1 1 1 81.3 50
81.3
A-P001 0.25
4.8 1.568616
1 81.3 50 81.3
A-P001 1
18 2.890372
1 81.3 50
81.3
LNDV=Ln-transformed
con. (mcg/ml)
--
*Luann Phillips*| Director, Pharmacometrics
Cognigen Corporation, a wholly owned subsidiary of Simulations Plus, Inc.
1780 Wehrle Drive, Suite 110 | Buffalo, NY 14221-7000
Phone: 716.633.3463 x236 | Fax: 716.633.7404 |
[email protected] <mailto:[email protected]>
