I reviewed the probenecid and furosemide models with respect to OAT3 inhibition.
Both probenecid and furosemide are taken up into kidney cells via OAT3. Probenecid is a potent inhibitor of OAT3 (and therefore of its own uptake, theoretically).
In the naked probenecid model, uptake by OAT3 (Vmax) is optimized in the absence of an OAT3 inhibition process.
Then when modeled with furosemide, a potent OAT3 inhibition process is applied (which then inhibits probenecid uptake as well - a process not evaluated in the original probenecid model). This leads me to believe that the simulated PK profile of probenecid will be compromised in the DDI scenario.
Perhaps I have overlooked a key element. Thank you!
EDIT I see that the competitive inhibition process appears to not affect the concentrations of probenecid itself.
Hi all,
I reviewed the probenecid and furosemide models with respect to OAT3 inhibition.
Both probenecid and furosemide are taken up into kidney cells via OAT3. Probenecid is a potent inhibitor of OAT3 (and therefore of its own uptake, theoretically).
In the naked probenecid model, uptake by OAT3 (Vmax) is optimized in the absence of an OAT3 inhibition process.
Then when modeled with furosemide, a potent OAT3 inhibition process is applied (which then inhibits probenecid uptake as well - a process not evaluated in the original probenecid model). This leads me to believe that the simulated PK profile of probenecid will be compromised in the DDI scenario.
Perhaps I have overlooked a key element. Thank you!
EDIT I see that the competitive inhibition process appears to not affect the concentrations of probenecid itself.
Paul