How to handle plasma protein binding in a cancer population when the main binding protein is unknown in PK-SIM?

[NingJia012]

Hello everyone,

I am using PBPK modeling to perform preclinical-to-clinical extrapolation and predict the exposure of an anti-cancer small molecule in chinese cancer population. The compound is a lipophilic weak base, with high plasma protein binding.

In our in vitro studies, we only measured the overall plasma protein binding without identifying the main binding protein. Therefore, I set the binding protein to "unknown" for all species in the model.

According to the PK-Sim documentation, when the binding protein is set to "unknown", the model no longer considers changes in protein concentration with age. However, in cancer patients, albumin levels are often decreased and AAG levels are increased.

In this situation, when I want to predict exposure in chinese cancer population, how should I change the protein binding-related parameters?

Thanks!

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