P-gp and specific binding query

[meensrinivasan]

Hello,

I'm trying to replicate a prior PBPK model of Digoxin. The publication mentions ATP1A2 Koff and Kd values and P-gp Km and Kcat.

In the compounds- distribution- specific binding- protein binding partners tab, I entered the values for ATP1A2 Koff and Kd

In the transport and excretion- transport proteins tab, I selected "specific active transport" and entered values for p-gp Km and Kcat. How do we decide whether to use -Intrinsic active transport - MM

• Specific active transport - MM
• In-vitro active transport - MM?

Then, in the individual (expression) tab, I added transport protein for p-gp and expressed it 100% in the kidney. The transporter showed up as "Efflux" by default and then I changed it to P-gp type. Also added ATP1A2 as the protein binding partner with reference conc and expressed it 100% in brain.

Added the administration protocol and ran a simulation.

In the create simulation tab, there was a warning near specific binding. But its showing up as transporter in individual. Anything that I'm missing here?

Also the reaction diagram doesn't mention P-gp.

My simulation resulted in the following plot

The model seems to have over predicted the Cmax values. Have I made a mistake somewhere while entering the values for P-gp?

Any help will be greatly appreciated!! Thank you!

[msevestre]

@ms-12345 Thanks for posting. If you want to increase your chance of getting an answer to your question, I'd suggest to post your question in the FORUM. The issues here are solely for release planing and bug reporting.

My suggestion would be to

1. Create a new entry in the forum with the exact same content as this one (do not link the issues, simply duplicate the content)
2. Close this issue

Cheers,

[meensrinivasan]

Sure, thank you!