Date: Tue, 04 Apr 2000 13:01:50 -0400
From: Raj <nagaraja@ufl.edu>
Subject: zero order and bolus input

Dear NM users,
I am trying to fit (ADVAN 6) a dataset containing both iv bolus at time=0 and and an iv infusion from time 1 to 24 h. I am using the control stream as follows. If you could please suggest me if it is right.

In the dataset, EVID is given as 1 for dose item and 0 for DV item. Also, AMT and RATE are given as, say 10000 and 434.8, respectively, for the infusion and rate is given as 0 for IV bolus.

Many thanks for the help

Raj

$PROBLEM DRUG SAMPLE PLASMA LEVELS (3 SUBJECTS)
$INPUT ID TIME AMT DV RATE EVID
$DATA SAMPLE.CSV

$SUBROUTINE ADVAN6 TRANS1 TOL=3
$MODEL
COMP=(CENTRAL)
COMP=(PERIPH)

$PK
TVCL = THETA(1)
TVV1 = THETA(2)
K12 = THETA(3)
K21 = THETA(4)

CL=TVCL*EXP(ETA(1))
V1=TVV1*EXP(ETA(2))
S1=V1

$DES
DADT(1)=-CL/V1*A(1)+ K21*A(2)-K12*A(1)
DADT(2)= -K21*A(2)+K12*A(1)
$THETA
(0.1, 15)
(0.1, 30)
(0.00001 1.5)
(0.00001 0.8)

$OMEGA
0.5 ; FOR CL
0.6 ; FOR V1

$ERROR
Y=F *(1+EPS(1))
IPRED=F
IRES=DV-IPRED


$SIGMA 0.4

$ESTIMATION METHOD=1 MAXEVAL=9999 PRINT=5
$TABLE ID TIME AMT DV TVCL CL TVV1 V1 K12 K21 IPRED IRES
NOPRINT ONEHEADER FILE=SAMPLEOUTPUT