time-controlled drug delivery
From: musor000@optonline.net
Subject: [NMusers] time-controlled drug delivery
Date: Sat, March 20, 2004 3:59 pm
Dear NONMEM users,
I try to replicate a model of time-controlled drug delivery. Infusion rate is
an oscillating function. Predicted variable does not match the observed one
well. Surprisingly, when I add a data record with time=0 and missing dependent
variable, I receive different results. Objective function is negative. Also,
when I use TIME instead of T in $des block, results are different. The code
and the data are below.
Thanks you,
Pavel
$PROB TIME-CONTROLLED DRUG DELIVERY, SINGLE SUBJECT
;RESULTS ARE QUITE DIFFERENT WHEN I SPECIFY MISSING
;RECORD FOT TIME=0. STRANGE...
$INPUT EVID TIME CP=DV
$DATA PK36DIF0.DA
$SUBROUTINES ADVAN8 TOL=7 ;TOL - THE NUMBER OF ACCURATE DIGITS
$MODEL COMP=(DEPOT)
$EST MAXEVAL=9990 SIG=7 PRINT=5
$PK
AMPL =THETA(1) ;AMPLITUDE OF OSCILATIONS
V1 =THETA(2) ;VOLUME OF DISTRIBUTION;
K1 =THETA(3)
S1 =V1 ;The amount A in the observation compartment
;at the time of observation, divided by the
;value of a parameter S, is used as the prediction.
CL=K1*V1
$THETA (.01,0.35,1) ;AMPL
(.1,2,10) ;V1
(.001,0.025,100) ;K1
;$OMEGA DIAGONAL(7) .1 .1 .1 .1 .1 .1 .1
$DES
TM=T
RIN=0.1+AMPL*0.1*COS((2*3.14159265/60)*(TIME-60))
DADT(1)=0.1+AMPL*0.1*COS((2*3.14159265/60)*(T-60))-K1*A(1)
$ERROR
Y=F+ERR(1)
CONC=F
$OMEGA 0.1
$COV ;COVARIANCE STEP IS IMPLEMENTED
$TABLE TM AMPL V1 K1 CL NOAPPEND FIRSTONLY
$TABLE TM TIME PRED DV RIN RES WRES
$SCAT DV VS IPRED UNIT
*******************
DATA:
0 10.6061 0.5173
0 31.8182 0.8214
0 60.1010 1.8692
0 77.7778 1.4870
0 91.9192 1.4728
0 120.2020 2.4959
0 152.0202 1.5575
0 201.5152 1.5988
0 229.7980 2.3068
0 300.5051 2.5459