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The following message was posted to: PharmPK
Dear PharmPK 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 (I'm
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 user's guide)?
I would really appreciate if anybody could clarify what I'm doing wrong.
Thanks a lot for your help!
Best regards
Nele
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The following message was posted to: PharmPK
Dear all who answered to my question,
thank you very much for your input, it all helped a lot. I now used the
proper coding for infusion and left out the estimation for KA, and it
ran
beautifully.
I'll get back to you when problems get more complicated :-)
Thanks again
Nele
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Dear Nele,
Try the following parameters. They worked well on my computers. But I
do not know whether your input is bolus. If you want to tell program
how long the drug was applied for, you could enter 2 events: one is a
rate ( e.g. 1200) and another is a rate 0.
If the RATE is 1200, the design matrix is near singular.
number of model inputs:1
number of bolus inputs:1
compartment number for each bolus input:2
number of imput event times:1
input event: (r is rate, b is bolus)
0,0,1200
output equations:1
number of model output equations:1
number of sample times: 8
0, 0.5, 1, 1.5, 2, 3, 6, 8, all to be optimized...ok
constraints (lower, upper):0,0
CL=6.6, Vc=36.6, KA=1.91, CLd=18.5, Vp=33.1, all to be estimated...ok
IC (0,n)
SDinter was 0.01 and
SDslope was 0.166
1000 interations
Yours Sincerely
Ma Guangli
Ph.d. Candidate.
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Copyright 1995-2010 David W. A. Bourne (david@boomer.org)