Re: 3 compartment nonlinear pharmacokinetics model
From: "Yungwei Hsu" <hsu00013@mc.duke.edu>
Subject: Re: [NMusers] 3 compartment nonlinear pharmacokinetics model
Date: Wed, 14 Nov 2001 17:08:02 -0500
Dear Dr. Holford,
Thank you very much for your generous help.
After running the NONMEM, I got
V1 V max Km V2 CL2 V3 CL3
5.83 1.17 0.746 121 0.630 37 1.23
and the following message
======================================
MINIMIZATION SUCCESSFUL
NO. OF FUNCTION EVALUATIONS USED: 1038
NO. OF SIG. DIGITS IN FINAL EST.: 3.1
S MATRIX ALGORITHMICALLY SINGULAR
T MATRIX SET EQUAL TO RS*R, WHERE S* IS A PSEUDO INVERSE OF S
===================================================================
What does this means? My control file is as follows,
==========================================
$PROBLEM 3 COMPARTMENT Nonlinear Kinetics Modeling
$INPUT ID TIME AMT=DOSE CONC=DV RATE
$DATA input10
$SUBROUTINES ADVAN6 TOL=5
$MODEL COMP (ONE) COMP (TWO) COMP (THREE)
$PK
V1=THETA(1)*EXP(ETA(1))
VMAX=THETA(2)*EXP(ETA(2))
KM=THETA(3)*EXP(ETA(3))
V2=THETA(4)*EXP(ETA(4))
Q2=THETA(5)*EXP(ETA(5))
V3=THETA(6)*EXP(ETA(6))
Q3=THETA(7)*EXP(ETA(7))
$DES
DC1=A(1)/V1
DC2=A(2)/V2
DC3=A(3)/V3
CL=VMAX/(KM+DC1)
DADT(1)=Q2*DC2 + Q3*DC3 - (Q2 + Q3 + CL) *DC1
DADT(2)=Q2*(DC1-DC2)
DADT(3)=Q3*(DC1-DC3)
$ERROR
C1=A(1)/V1
Y=C1*EXP(ERR(1)) + ERR(2)
$THETA
7.41
1.79
1.95
27.7
1.14
115
0.8
$OMEGA1 0.1 0.1 5 0.1 2 0.1
$SIGMA 0.1 0.1
$COVAR UNCONDITIONAL
$EST SIG=3 MAX=3000 PRINT=5 NOABORT METHOD=0
;$MSFI=ms2 POPETAS=6