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#1 Angus McLean

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Posted 01 October 2013 - 04:32 PM

..have single dose plasma concentrations and I want to fit them to a one compartment model with a lagtime with a view to performing a multiple dose simulation.

The plasma concentration time worksheet was imported and connected to the PK MODEL OBJECT.

I have fitted plasma concentration time data to a 1 cpt model with first order absorption and first order elimination with a lagtime. I used initial estimates and I got the program to provide the fit and the parameters I need for a multiple dose simulation.

I have disconnected the original worksheet with the plasma concentration time (from the single dose) from the NCA object.[ is this a blunder?].

I have the multiple dose Table imported as a worksheet and I have used this worksheet for pointing (CONNECTING) to the dose for the NCA model object. The doses are set correctly to ng.

I have also imported a new Table of Times I want the simulations to be made at. This is a column of time (x values) in hours.

Now for the simulations I have eliminated the lagtime and set the modet to run as a 1 cpt model first order elimination and first order absorption.

I find that the simulation runs and it uses the times I want but the values of y (should be ng) are ridiculously high. The pattern of the predicted profile for the multiple doses (y axis) is correct , but the scale is absurd and I do not know why.

 

I have seen this problem before, but I cannot remember what the cause is. I have checked the doses and the units are ok (ng). I am baffled since this is so routine and yet I cannot get it to work.

 

Please can be advised accordingly,

 

 

Angus



#2 Angus McLean

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Posted 01 October 2013 - 06:15 PM

I should have said I am using the cla ssic WiNonLIN models. I have jsut tried another similar simulation and I am getting the sameresult. That is the y scale is all wrong, but the shapeof the model predicted concentrtions is fine.

 

So the problem relates to some thing related to y aling. and I cannot see what it is. I do rember I had this problem before but I do not remember the solution. So i am doing something that previuous users of WinNonlin will do.

 

I have been tryng for 4-5 hours something I could do in Winonlin i~ 30 ,minutes.

 

 

Angus



#3 Simon Davis

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Posted 01 October 2013 - 06:22 PM

did you scale dose to same units as conc when fitting?



#4 Angus McLean

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Posted 01 October 2013 - 07:08 PM

Here is what I just did: I did a fitting to a series of ng concentration (y scale) and X (Time scale) in hours at 20000000 ng dose (20 mg). It is just fine. Then I check the simulation box and run it again to see a simulation at the same dose. and I get a bizarre result the y scale is much much higher.

 

Angus



#5 Simon Davis

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Posted 01 October 2013 - 10:57 PM

angus please can you post the project or if confidentiality is an issue, email support and reference this thread?

 

 thanks, Simon.

 

PS onthe road this week so sorry for the short responses



#6 Angus McLean

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Posted 02 October 2013 - 09:55 AM

Simon: So,me of the time it works and some not. I am thinking I am getting my wires crossed here. The odd thing is after fitting it does a simulation adn gives the correct profile shape, but the y axis is out of line.

 

I have found somthing not to do and I will explroe fiurther to give you better information.

 

One thing I am findingf useful is to use CTRLC (COPY) and CTRLV(PASTE) usefulwhen working with the program.

 

 

Thanks ,

 

Angus



#7 Angus McLean

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Posted 09 October 2013 - 02:18 PM

Simon: what I think caused this problem is that when one is fitting with multiple doses there is a window (weighting dosing options) provided for one to stipulate the number of doses. You should enter the number of doses there.

 

 

What I was doing was thinking you had to create a dose Table for the multiple doses and use that Table. So I was geting my wires crossed here!

 

Thanks,

 

Angus



#8 Simon Davis

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Posted 09 October 2013 - 02:27 PM

So are you good now?

 

I'm not sure I followed your problem but if you're happy now then the problem is resolved.

 

 Simon






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