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number of UIR exponentials

UIR exponential

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#1 Ravi kumar

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Posted 29 August 2018 - 11:23 AM

In Phoenix winonlin IVIVC we are stuck with the selection of UIR exponentials. Can we get an explanation regarding the number of exponentials application with respect to formulation  for invivo data (in order to generate UIR)?

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#2 Simon Davis

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Posted 29 August 2018 - 11:29 AM

Have you plotted the data (semi-log scale)?  you are looking at the number of compartments exhibited by your compound.  e.g if you think it is definitiely one compartment you might force this  'Max number of UIR exponentials' to 1.

 

 Simon.



#3 Ravi kumar

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Posted 29 August 2018 - 11:44 AM

Thank you Mr Simon,

 

Could you please elaborate is there any relationship between selection of UIR exponentials and compartment model.

 

If one compartment model which UIR exponential to be selected

 

If two compartment model which UIR exponential to be selected

 

If I am not wrong compartment model selection is purely based on API/formulation characteristics right?.

 

Based on API/formulation we need to decide compartment modelling and followed by selection of corresponding UIR exponential. Is it right?.

 

Thank you

 

 



#4 Simon Davis

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Posted 01 September 2018 - 06:15 AM

Sorry Ravi,I thought I already replied to you but it seems my answer wasn't saved.

 

the UIRs are looking for the intercept and slope from either a macro constant parametised model and/or secondary parameters; you cna use WNL classic or Phoenix models for this.

 

  i.e. If a one compartment model, then UIR would be defined by A1 and alpha1; intercept and slope.

 

 

Lastly the assumption for UIR is that the compartment model is based on the API characteristics, basically if you give ideally an IV bolus, you see the processes by which it is distributed and eliminated.  You can use these with deconvolution to better understand absorption processes.

 

Then you can use these to inform the formulation characteristics to e.g. get extended release, match innovator etc.

 

  Simon.







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