How to include 'user defined variability' in population PK modeling for 'kcat', which is 'obtained by PI'?

[arketkar]

Hi!

In one of the models, I incorporated 'in-vitro Vmax' and 'Km' values generated using a recombinant CYP. Then I optimized the 'kcat' value by Parameter Identification (PI) to fit to the observed data. While running a simulation for a population I wanted to incorporate some variability (as SD) for the 'kcat' value. However under the 'user define variability' I am seeing only the 'in-vitro Vmax' and 'Km' parameters, and not the 'kcat' obtained by PI. In such a case 'in-vitro Vmax' has no effect, as that has been taken over by 'kcat'. Can someone suggest me the way to incorporate variability for 'kcat' in such a case? Thanks in advance. Anant

[NinaHanke]

Dear Anant,

You could add variability on the reference concentration of your CYP (in your population under "user defined variability"). We use "log normal" distribution with a GeoSD from literature. BUT if you selected "Ontogeny/variability like CYP..." in the individual that you built your population from,

it should already have variability in your population. You can check that in your population under "Distribution->Ontogeny factor".

Yours, Nina

[arketkar]

Dear Nina,

Thank you so much for those inputs.

I have selected "Ontogeny/variability like CYP..." in the individual. So the variability as highlighted by you would work in my case.

Thanks once again.

Regards. Anant