3 replies to this topic

[Al Corey]

Does anyone have any tips on implementing a physiologocally based PK model in Phoenix NLME?

 

Thanks,

 

Al

[Al Corey]

Perhaps my initial question was too braod. As a side project, I am attempting to implement the platform PBPK model for monoclonal antibodies of Shah and Betts (JPP 2012, 39:67-86) using Phoenix NLME. With just the tissue level plasma and lymph flows constructed using the graphical interface (ie, not having included the blood cell components or interstitial, endosomal, and cellular spaces of the published model), it already seems that the maximum allowed number of equations will be exceeded. Since this is my 1st attempt at creating a PBPK model in Phoenix NLME, are there any tricks or tips of which I should be aware? For example, it seems that NLME utilizes 1 parameter for the flow into a tissue, and a separate parameter for the flow leaving that tissue. It seems that a reasonable alternate would be to code the flow out of the tissue as the in flow minus the lymphatic out flow - but I'm not sure NLME accepts that coding. In short, any guidance, examples, hints or tips would be appreciated.

 

Thanks,

 

Al

[Simon Davis]

Hi Al,

    I personally haven't done much PBPK modelling but I can perhaps make an initial response to your questions.

 

1) what version are you running, Phoenix 6.3 permits and expanded number of equations so if you haven't upgraded that may well help. (QC10923)

 

2) I believe in textual mode you should be able to consolidate the 1 parameter for the flow into a tissue and a separate parameter for the flow leaving that tissue into one.

 

Thanks,

 

 Simon

 

PS I should also add that a technical constraint of this forum platform is we can haven't got a way to send out a digest of the week's conversations, so unless people actively log in they won't have seen you question. We are hoping to address that with an upgrade over the summer.

[Al Corey]

Thanks for the feedback. We haven't upgraded to version 6.3 yet, so I'll follow-up on that. I have been working in textual mode to consolidate flows; can't report any success yet, since I'm still debugging the code. Currently, I'm trying to just get a very simplified PBPK model working with code that uses the fewest parameters possible (ie, 1 flow for both in and out of a tissue). When completely stumped, I'll post the textual model for critique (and then likely find out I made a really basic mistake, but that's learning).

 

Al