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The difference of AUC value between NCA and Monte Carlo simulation based on Pop PK model

NLME modelling and simulation

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#1 Harper

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Posted 13 December 2021 - 04:54 PM

Dear all.
 
     I used Phoenix NLME to successfully build a 2 compartment combining residual Pop PK model with lag time, and implemented Monte Carlo simulation to calculate AUC values based on this, but found that the results calculated by Pop PK model are very different from those based on NCA method.  
 
     However, it should be noted that the database characteristics of the 3000 virtual individuals used in the simulation were copied from the modeling database, which may exclude this effect.
 
     I'm a beginner and I would appreciate if you could help me, even if it's just a rough guide.
 
     Thanks in advance. 

Edited by Harper, 19 December 2021 - 05:45 AM.

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#2 Harper

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Posted 15 December 2021 - 05:11 AM

 

Dear all.
 
     I used Phoenix NLME to successfully build a 2 compartment combining residual Pop PK model with lag time, and implemented Monte Carlo simulation to calculate AUC values based on this, but found that the results calculated by Pop PK model are very different from those based on NCA method.  
 
     However, it should be noted that the database characteristics of the 3000 virtual individuals used in the simulation were copied from the modeling database, which may exclude this effect.
 
     I'm a beginner and I would appreciate if you could help me, even if it's just a rough guide.
 
     Thanks in advance. 

 



#3 Simon Davis

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Posted 15 December 2021 - 05:22 PM

Hi Harper, your code uses;

 

deriv(AUC = C)

 

 so you need to be carefuly becase this is being integrated over time so when you requested it in your table you need to make sure you are comparing a large time to be comparable with the NCA generated AUCinf (or AUClast).

 

see the table below where I compare AUC at 24, 999 and 9999.

 

At first glance, I am not sure your model is capturing the sustained absorption, what is the mechanism of delivery, maybe a Zero order might help?

 

 Simon.

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  • compare_AUC.jpg






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