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Open-Systems-Pharmacology / PK-Sim

PK-Sim® is a comprehensive software tool for whole-body physiologically based pharmacokinetic modeling
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Interstitial Unbound larger than Interstitial Concentration #3004

Open falkenhagen opened 1 week ago

falkenhagen commented 1 week ago

The "Brain Interstitial Unbound Concentration" (calculated using the default Observer) is larger than the" Brain Interstitial Concentration" for some drugs. One example is the Gabapentin model published in the CKD-Qualification: https://github.com/Open-Systems-Pharmacology/Qualification-CKD/tree/main/Qualification/Input/Models.

Looking at the Observer definition in MoBi (also described in this Discussion Topic: https://github.com/Open-Systems-Pharmacology/Forum/discussions/1167), the Interstitial Unbound Observer depends on the "Partition coefficient (interstitial/water)". Based on the two Formulas from the Screenshots below and the default values of the drug-independent parameters

the parameter "Partition coefficient (interstitial/water)" becomes larger than 1 whenever the fraction unbound (plasma) is above ~91.5% ( in this case). Should this parameter be capped at 1? Or is there an issue with the Formulas?

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RobinM92 commented 2 days ago

@PavelBal @msevestre We posted this here as it seems more a bug than an actual discussion point, I guess it's it not desired to have fractions unbound higher than 100%? Or should we change this to a discussion on the forum?