Metabolite kinetics help
From:"Bonate, Peter"
Subject:[NMusers] Metabolite kinetics help
Date:Fri, 28 Jun 2002 09:27:51 -0500
I was wondering if I could solicit some help from the group. I'm trying to model parent and metabolite
kinetics. Parent consists of 2-compartments and metabolite consists of 1-compartment. The starting
values for parent are based on ADVAN3 results. The starting values for metabolite parameters were
based on trial and error within SAAM II to give reasonable observed metabolite concentrations. Sigma
is large due to some previous errors where it was suggested to raise the starting value of sigma. Here
is my control stream:
$PROBLEM ADVAN9 P+M
$DATA PMCOV.DAT IGNORE=C
$INPUT PTID=ID CYCL DAY HR TIME DV DOSE AMT RATE EVID MDV
LYM WBC HO CMT TYPE L2=DROP
AP HGB HCT NEUT PLAT=DROP RACE=DROP AGE=DROP
$SUBR ADVAN9 TRANS1 TOL=4
$MODEL NCOMP=3 COMP=(CENTRAL) COMP=(PERIP) COMP=(M)
$PK
CL = THETA(1)*EXP(ETA(1))
V1 = THETA(2)*EXP(ETA(2))
Q = THETA(3)
V2 = THETA(4)
FM = THETA(5)
KELM = THETA(6)
S1 = V1/1000
S3 = 1
$ERROR
IPRD = F
IF (CMT .EQ. 1) THEN
Y = F*EXP(EPS(1)) + EPS(2)
ELSE
Y = F*EXP(EPS(3)) + EPS(4)
ENDIF
$THETA
(0, 41.1, 600); THETA(1) CL
(0, 90.8, 1500); THETA(2) Vc
(0, 70.1, 1000); THETA(3) CL
(0, 232, 1500); THETA(4) Vp
(0, 0.001, 1); THETA(5) FM
(0, 0.2, 1); THETA(6) KELM
$DES
DADT(1) = -(CL + Q)*A(1)/V1 + Q/V2*A(2)
DADT(2) = Q/V1*A(1) - Q/V2*A(2)
DADT(3) = FM*CL/V1*A(1) - KELM*A(3)
$OMEGA 0.267
$OMEGA 0.211
$SIGMA 5 0.00001 FIXED
$SIGMA 5 0.00001 FIXED
$COV
$EST MAXEVAL=9999 SIGDIGITS=4 NOABORT METHOD=CONDITIONAL INTERACTION POSTHOC
I keep getting this error message:
0PRED EXIT CODE = 1
0INDIVIDUAL NO. 2 ID=0.20000000E+01 (WITHIN-INDIVIDUAL) DATA REC NO. 3
THETA=
4.11E+01 9.08E+01 7.01E+01 2.32E+02 1.00E-03 2.00E-01
OCCURS DURING SEARCH FOR ETA AT A NONZERO VALUE OF ETA
ERROR IN LSODI1: CODE 205
0END OF MESSAGES
Here is the data for individual 2. I've ripped out the covariate columns
PTID CYCLE DAY HR TIME DV DOSE AMT RATE EVID MDV CMT TYPE
2 1 1 0 0 . 27 27 27 1 1 1 1
2 1 1 0 0 0 27 . . 0 1 1 1
2 1 1 1 1 83.6 27 . . 0 0 1 1
2 1 1 1 1 4512 27 . . 0 0 3 2
2 1 1 2 2 37.1 27 . . 0 0 1 1
2 1 1 2 2 5327.5 27 . . 0 0 3 2
2 1 1 3 3 23.4 27 . . 0 0 1 1
2 1 1 3 3 5979.8 27 . . 0 0 3 2
2 1 1 4 4 0 27 . . 0 1 1 1
2 1 1 4 4 5599.3 27 . . 0 0 3 2
2 1 1 5 5 10.6 27 . . 0 0 1 1
2 1 1 5 5 5599.3 27 . . 0 0 3 2
2 1 1 24 24 3479.2 27 . . 0 0 3 2
2 1 2 0 24 . 27 27 27 1 1 1 1
2 1 2 0 24 0 27 . . 0 1 1 1
2 1 2 1 25 147.5 27 . . 0 0 1 1
2 1 2 1 25 8426.1 27 . . 0 0 3 2
2 1 3 0 48 . 27 27 27 1 1 1 1
2 1 4 0 72 . 27 27 27 1 1 1 1
2 1 5 0 96 . 27 27 27 1 1 1 1
Can someone tell me what I am doing wrong and what this error message means. Thanks ALOT!
pete
Peter L. Bonate, PhD
Director, Pharmacokinetics
ILEX Oncology, Inc
4545 Horizon Hill Blvd
San Antonio, TX 78229
phone: 210-949-8662
fax: 210-949-8487
email: pbonate@ilexonc.com