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How does the log(Ko/w) influence the fraction unbound to Albumin ? #706

Closed jonathanlsn closed 3 years ago

jonathanlsn commented 3 years ago

Hello, I made two models for the same molecule on Mobi. The Only difference is the log(Ko/w) value I set to 4.7 for the first one and to 3.8 for the second one. I saw that the Fraction Unbound to Albumin was different either : 0.01 and 0.03 respectively.

I also tried to modify the parameter of the second model by setting the Fraction unbound to 0.01 (as the first one) and I obtain very different results. So I suppose this fraction unbound has a great influence on the simulation and I was wondering how does the log(Ko/w) influence in the calculation of the fraction unbound to Albumin ?

StephanSchaller commented 3 years ago

I was wondering how does the log(Ko/w) influence in the calculation of the fraction unbound to Albumin ?

It doesn't. Fraction unbound (fu) is a measured input parameter. But of course, log(Ko/w) and fu both influence the distribution of the molecule.

To learn more, I suggest to check out the literature on the basics of compound distribution and compartmental partitioning: https://docs.open-systems-pharmacology.org/working-with-pk-sim/pk-sim-documentation/pk-sim-compounds-definition-and-work-flow#adme-properties

Hope this helps.

Best, Stephan

jonathanlsn commented 3 years ago

Indeed, I checked the equation for the calculation of fu and the Log(ko/w) doesn't appear but have an indirect influence on fu through the calculation of logD_pH_7p4.

Thank you for your help !

Best, Jonathan