- On 18 Apr 2006 at 17:16:24, nplock.-a-.zedat.fu-berlin.de sent the message

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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 - On 19 Apr 2006 at 08:48:50, nplock.-a-.zedat.fu-berlin.de sent the message

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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 - On 19 Apr 2006 at 20:08:26, "Ma Guangli" (guanglima.aaa.gmail.com) sent the message

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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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