RE: COEFFICIENT MATRIX IS ALGORITHMICALLY SINGULAR
From:"Kazimierz H.Kozlowski" khkoz@czd.waw.pl
Subject: RE:[NMusers] COEFFICIENT MATRIX IS ALGORITHMICALLY SINGULAR
Date: Wed, August 11, 2004 3:31 pm
Dear Dr Nandy,
You probably need some simplificate of your codes
i.e. one compartment model I suggest because
it is zero order input and F1 is V1/F as sinkle parameter.
I'm not sure, but F1 factor not act for infusion and
if you need estimate, it could be S1=V1/F1/1000
but simultaneous oral and i.v. data are need.
It is good to avoid 0 values for clearaces and rate constant.
Your code I see as the above:
sincerely yours
Kazimierz H. Kozlowski
Laboratory of Pharmacokinetics
The Childrens Memorial Health Institute
Warsaw, Poland
$PROBLEM $INPUT C TIME DV SUBJ ID AMT TYPE EVID MDV CMT RATE TAMT AGE HT
WT SA SEX RCE
$DATA C:\ IGNORE=C
$SUBROUTINES ADVAN5
$MODEL COMP=(CENTERAL,DEFDOSE DEFOBS)
$PK
CLS=THETA(1)*EXP(ETA(1)) ; Induced Clearance
CLI=THETA(2)*EXP(ETA(2)) ; Baseline Clearance
KOUT=THETA(3)*EXP(ETA(3)); Turnover rate
LAG=THETA(4)*EXP(ETA(4))
NEWT=TIME-LAG
IF (NEWT.LE.0) NEWT=0
CL10=CLS-((CLS-CLI)*EXP(-KOUT*NEWT))
TVV1=THETA(5)
V1=TVV1*EXP(ETA(5))
D1=THETA(6) ;Duration of zero-order input
;==========================================================================
;F1=THETA(7) ; Bioavaialbility factor
;probably F1 is not active for infusion input (please check)
===========================================================================
K10=CL10/V1
S1=V1/1000
;===========================================================================
;S1=V2/F1/1000 ;probably F1 is not active for infusion input (please check)
;or
;S1=V2*F1/1000 ;probably F1 is not active for infusion input (please check)
;===========================================================================
$ERROR
FX=0
IF(F.EQ.0) FX=1
W=F+FX
Y=F*(1+ERR(1))+ERR(2)
IPRE=F
IRES=DV-IPRE
IWRE=IRES/W
$THETA
(1,100) ;CLS - clearance after induction
(1,500) ;CLI - clearance before induction (base-line clearance)
(1,300) ;KOUT - induction constant
(6,172) ;LAG - lag-time for induction of CL10
(1,800) ;V1/F1- volume of distribution
(1,10) ;D1 - duration of zero-order absorption
;(0,0.5,1) ;F1 - bioavailability factor - could be estimated with
additional
;iv data
$OMEGA .5 .5 .5 .4 0.5
$SIGMA 0.2 5
$ESTIMATION MAXEVAL=9999 PRINT=5 NOABORT METHOD=1 INTERACTION
$COV
$TABLE ONEHEADER NOPRINT FILE=C:\*.tab ID TIME DV SUBJ AMT CL10
V1 ETA(1) ETA(2) ETA(3) IPRE K10
D1
; F1 ==========================
$SCATTER PRED VS DV UNIT BY CMT
$SCATTER RES WRES VS PRED TIME ORD0 BY CMT $SCAT PRED DV VS TIME BY CMT
$SCATTER IPRE VS DV UNIT BY CMT