From: kmanouil@unmc.edu
Subject: Sequential absorption processes with lag time
Date: Thu, 4 Oct 2001 11:58:01 -0500
Dear NONMEM users,
I read discussion ?modeling fast and slow absorption? back to 1995.
Currently, I have similar type of problem.
There is one-compartment model with two absorption compartments linked
together by zero-order rate. A drug dosed in one of depot compartments.
Absorption from the second compartment had delay in a time.
So far I used ADVAN6 with two depot compartments and central compartment.
Despite, the fact that the problem was solved with WinNonlin,
I cannot figure out how to code time delay in NONMEM.
Can you help me with advice?
Konstantine Manouilov
Research Associate
University of Nebraska Medical Center
Sequential absorption processes with lag time
From: "Piotrovskij, Vladimir [JanBe]" <VPIOTROV@janbe.jnj.com>
Subject: RE: Sequential absorption processes with lag time
Date: Mon, 15 Oct 2001 13:42:47 +0200
Konstantine,
You can try the following control which implements the sequential zero-order
-- first-order absorption with the lag time.
$PROBLEM Delayed absorption
$INPUT ID TIME AMT RATE CONC=DV
$DATA nmd.txt
$SUBROUTINES ADVAN2 TRANS2
$PK
CL = THETA(1) * EXP(ETA(1))
V = THETA(2) * EXP(ETA(2))
D1 = THETA(3) * EXP(ETA(3))
KA = THETA(4) * EXP(ETA(4))
ALAG1 = THETA(5) * EXP(ETA(5))
S2 = V
$ERROR CALLFL=0
IPRE = F
Y = IPRE * EXP(ERR(1))
$THETA
(0 3 10); 1 CL
(1 100 ); 2 V
(0 .5 5); 3 D1
(0 1 2); 4 KA
(0 .5 1); 5 ALAG
$OMEGA .1 .1 .1 .1 .1
1 2 3 4 5
$SIGMA .05
$EST MSFO=msf MAX=9990 PRINT=10 POSTHOC
$COV
$TABLE ID TIME AMT IPRE FILE=tab.txt NOPRINT ONEHEADER
$TABLE ID CL V D1 ALAG1 AMT FILE=prm.txt NOPRINT ONEHEADER NOAPPEND FIRST
An example of a (single-individual) data set is given below. It can be used
for simulations (DV variable is dummy). Note RATE = -2 for the dose record
to allow estimating zero-order absorption duration D1.
1 0 10 -2 0
1 0.1 0 0 1
1 0.2 0 0 1
1 0.5 0 0 1
1 1 0 0 1
1 2 0 0 1
1 4 0 0 1
1 8 0 0 1
1 16 0 0 1
1 24 0 0 1
1 48 0 0 1
Best regards,
Vladimir
------------------------------------------------------------------------
Vladimir Piotrovsky, Ph.D.
Research Fellow
Advanced Modelling and Simulations
Global Clinical Pharmacokinetics and Clinical Pharmacology (ext. 5463)
Janssen Research Foundation
B-2340 Beerse
Belgium
Email: vpiotrov@janbe.jnj.com