# Sequential PK PD

From: Indranil Bhattacharya <ibhattacharya>
Date: Wed, 10 Feb 2010 00:04:48 -0500

Hi, I have a question regarding how NONMEM reads the code when doing a
sequential PK/PD run.
I fit the PK data (extravascular admin) using a KOKA model with sequential
absorption. The data was based described by this sequential model where K0
process starts after Ka. To fit the data I used ADVAN4 TRANS4 (2 COMP
model).
Now the next step is to fit the PD data and here is where I am confused.
For the PK parameters I designate them under \$PK as shown in the code
provided. CL and V2 had individual values which were included in the data
set. Also in the PD data was set up to show zero and first order absorption
(2 dosing lines, RATE=0 or RATE=-2, COMP#)
Question -1- Does NONMEM understand that K0 values are to be calculated
from F2.DOSE/D2 or should I have to provide it in the data set ?
Question-2- For ALAG1 and ALAG2 again, does NONMEM understand how to use
them or I have to specify that under \$DES using IF (T.LE.ALAG1) etc.?

\$MODEL
NCOMP=5
COMP=(DEPOT,DEFDOSE)
COMP=(CENTRAL)
COMP=(TISSUE)
COMP=(RESPONSE)
COMP=(TISSUE)
\$PK
CL=CCL
V2=VV2
Q=0.01
V3=2.94
KA=0.004
K0=KK0
TLAG1=1.17
ALAG1=TLAG1
TLAG2=4.7
ALAG2=TLAG1+TLAG2
F1=0.7
F2=0.3
D2=108.96
S2=V2/1000

;PD MODEL

E0= THETA(1)
KIN=(THETA(2))*(EXP(ETA(1)))
KILL=THETA(3)*(EXP(ETA(2)))
K45=THETA(4)
K54=THETA(5)
KOUT=KIN/E0
A_0(4)=E0
A_0(5)=K45*E0/K54

\$DES
CONC=A(2)/V2
S=CONC

\$ERROR
EFF=LOG(A(4))
IPRED=EFF
Y=EFF+ERR(1)

Regards

Neil

--
Indranil Bhattacharya

Received on Wed Feb 10 2010 - 00:04:48 EST

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