Re: Different population estimates
From: Toufigh Gordi tgordi@buffalo.edu
Subject: Re: [NMusers] Different population estimates
Date: 11/17/2003 11:27 AM
Dear Leonid,
Doses were given as mg/kg and all the parameters are estimated on the
kg/basis. In the data file, subjects within the same dose group
get the same dose.
The model file is given below, in case there are any mistakes I am
making. I am assuming PRED is the population PK.
Toufigh
$SUBROUTINE ADVAN6 TRANS1 TOL=5
$MODEL NCOMP=2
COMP=CENT
COMP=PERIPH
$PK
VM=THETA(1)*EXP(ETA(1))
KM=THETA(2)
V1=THETA(3)*EXP(ETA(2))
Q=THETA(4)
V2=THETA(5)*EXP(ETA(3))
D1=DUR
S1=V1
BASE=THETA(6)*EXP(ETA(4))
IMAX=THETA(7)
IC50=THETA(8)*EXP(ETA(5))
HILL=THETA(9)
$DES
CON=A(1)/V1
DADT(1)=-A(1)*(VM/(KM+CON))/V1-A(1)*Q/V1+A(2)*Q/V2
DADT(2)=A(1)*Q/V1-A(2)*Q/V2
$ERROR
CONC=F
LAM=BASE-(IMAX*(CONC**HILL)/(IC50**HILL+(CONC**HILL)))
IF (PKPD.EQ.2) THEN
Y=LAM*(1+EPS(1))+EPS(2)
ELSE
Y=CONC*(1+EPS(3))+EPS(4)
ENDIF
$THETA (0, 7.02) ;1 VM
$THETA (0, 10.6) ;2 KM
$THETA (0, 4.42) ;3 V1
$THETA (0, 0.456) ;4 Q
$THETA (0, 33.7) ;5 V2
$THETA (0, 60.5, 100) ;6 BASE
$THETA (0, 56.6) ;7 IMAX
$THETA (0, 1.15) ;8 IC50
$THETA (0, 2) ;9 HILL
$OMEGA 0.07 ;1 IIV VM
$OMEGA 0.02 ;2 IIV V1
$OMEGA 0.12 ;3 IIV V2
$OMEGA 0.1 ;4 IIV BASE
$OMEGA 1 ;5 IIV IC50
$SIGMA 0.1 ;1 PROP ERROR PD
$SIGMA 1 ;2 ADD ERROR PD
$SIGMA 0.2 ;3 PROP ERROR PK
$SIGMA 0.1 ;4 ADD ERROR PK
$ESTIMATION NOABORT POSTHOC MAXEVAL=9999 PRINT=3 METHOD=1 MSFO=MSF1
$COVARIANCE
$TABLE ID TIME Y PKPD CONC NOPRINT ONEHEADER FILE=SDTAB1
$TABLE ID TIME BASE IMAX IC50 HILL VM KM V1 Q V2
NOPRINT ONEHEADER FILE=PATAB1