ADAPT II with SAMPLE option
From: nplock@zedat.fu-berlin.de
Subject: [NMusers] ADAPT II with SAMPLE option
Date: Tue, 18 Apr 2006 17:14:13 +0200 (CEST)
Dear NONMEM users,
I would like to ask you for your help concerning the software ADAPT II.
I have conducted a clinical trial with 34 individuals and would now like
to find out what were the informative sampling time points of the study.
It seemed to me like this should be possible using the SAMPLE option in
ADAPT II. Now to get familiar with the software I tried to use a simple
two compartment model coded with clearance terms. I chose 1 model input, 1
input event time, for which I entered a time (0) and a rate of 1200 (Im
still confused where to tell the software how long the drug is applied
for, because if I only put in a rate this does not really clarify how much
of the drug is given, or am I missing a point here? Could anybody comment
on that?). I then chose 1 model output equation with 8 observations at
time points 0, 0.5, 1, 1.5, 2, 3, 6, 8, all to be optimized. I entered
lower and upper time constraints (0,24) and then entered parameter values
(CL=6.6, Vc=36.6, KA=1.91, CLd=18.5, Vp=33.1, all to be estimated).
Initial conditions were all zero and not estimated. SDinter was 0.01 and
SDslope 0.166 (am I right that these corresponds to the square root of EPS
in NONMEM error model Y=IPRED+IPRED*EPS(1)+EPS(2)?) Then I chose D
optimality with maximum of 10000 iterations and got the result: Near
Singular Design Matrix. Can anybody tell me what my problem is? In
addition, is there any literature available on how to use the SAMPLE
option (because that is somehow neglected in the users guide)?
I would really appreciate if anybody could clarify what Im doing wrong.
Thanks a lot for your help!
Best regards
Nele