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ISEF optimization #509

Closed ckcho0625 closed 4 years ago

ckcho0625 commented 4 years ago

Hello, i have a question about IVIVE.

When i developed and confirmed PBPK model, metabolic fraction of CYP isoform is too much low than my expectation. I inputted Vmax and Km data in process type of 'in vitro metabolic rate in the presence of recombinant CYPs/enzymes - michaelis menten'

Results of intensive searching, i think that the cause is difference between rhCYP system and HLM system. So, i want to adjust ISEF factor for overcoming my problem. But, I didn't found methods to modify this factors. How can i adjust this factor? Where can i find this parameter? also i wonder default value of this parameter.

Thank you for your appreciation.

prvmalik commented 4 years ago

Hi,

There are no reliable methods for in-vitro-in-silico-extrapolation of Vmax for metabolism. However, the in vitro Km value does have some utility. The best way forward is to use the in vitro Km in your michaelis-menten approximation, then use the parameter identification tool to optimize the Vmax parameter.

Paul

StephanSchaller commented 4 years ago

Yes, and elaborating further on @prvmalik s great explanation, an ISEF factor is nothing more than a multiplication of your Vmax, so fitting Vmax (or "applying a factor that works") is the way to go.