Updates to the NONMEM adapter

[samjrrr]

Hello,

Thanks for the great library! I've recently been working with PyDarwin and getting some nice results.

We had some challenges when designing model spaces which were overcome using a modified version of the NONMEM adapter.

The features enabled with the NONMEM adapter modifications were:

• SAEM and IMP estimation methods which required MU referencing
• Variable number of transient absorption compartments which required dynamic rate constant and compartment count.

If you are interested, I would be happy to create a new branch and open a pull request with these modifications. I'll provide a little more detail about the implementation below.

Please let me know what you think. Thanks, Sam

Mu parameters

• Updating of mu parameters was completed in a similar fashion to how theta values are currently handled, e.g. mu template = MU(CL), mu model file = MU_1
• Mu parameters in the template:

• Mu parameters in the model file:

Dynamic rate constants

• Added RATE_CONSTANT as a new variable in the templates. This allows you to specify the rate constants by compartment name rather than number e.g Template = RATE_CONSTANT(DEPOT, TRANSIT1), Model file = k12 The compartment names are based on whatever the user defines at the start of the model file, e.g. for 'COMP = (DEPOT, INITIALOFF)' the compartment name would be 'DEPOT'.
• Rate constant in tokens:

• Rate constant in model file:

Dynamic compartment number

• Added NUMBER_COMPARTMENTS as a variable in the template. A user can specify NCOMP=NUMBER_COMPARTMENTS without knowing the final number of compartments we used this to add a variable number of transient compartments to the absorption model.

• Compartment count in template:

  

• Compartment count in model file:

  

[certara-msale]

Sam, Thanks for looking at this, sorry I'm just getting to this now. There is a branch called mu-referencing, we recognized that this would be something that users would need, just haven't gotten it into the master yet. But, we'd be very interested in your solution to this. WRT the templates, those are completely the users responsibility. That said, an example with a general solution to rates and number of compartments for ODEs would be great. So, yes, please fork it, and do a PR, we'll take a look. Mark

[samjrrr]

Hi Mark, Thanks for the message. Will hopefully have a pull request ready next month.

The other changes with dynamic rate constants and compartment numbers are not just a template convention they also involve modifications to PyDarwin. In both cases the user can enter a variable in the template rather than the actual number of compartments or the correctly numbered rate constant. PyDarwin substitutes these variables for the correctly formatted value expected by NONMEM. We used these dynamic variables to enable the addition of a variable number of transient compartments to our model space.

[certara-msale]

Thanks Sam, we'll look forward to seeing what you've done. It sounds useful, (although maybe a bit of a deviation from the general purpose architecture) Mark

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---

From: Sam Richardson @.> Sent: Thursday, March 28, 2024 9:37:49 AM To: certara/pyDarwin @.> Cc: Mark Sale @.>; Comment @.> Subject: Re: [certara/pyDarwin] Updates to the NONMEM adapter (Issue #73)

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Hi Mark, Thanks for the message. Will hopefully have a pull request ready next month.

The other changes with dynamic rate constants and compartment numbers are not just a template convention they also involve modifications to PyDarwin. In both cases the user can enter a variable in the template rather than the actual number of compartments or the correctly numbered rate constant. PyDarwin substitutes these variables for the correctly formatted value expected by NONMEM. We used these dynamic variables to enable the addition of a variable number of transient compartments to our model space.

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