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Are there specific and exclusive inhibitors of P-gp and CYP3A4 in
humans.
For instance if a drug is a substrate for both P-gp and CYP3A4, can the
contribution from inhibiting P-gp be separated from the inhibition of
CYP3A4.
Thanks
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The following message was posted to: PharmPK
Hi,
there are some "relatively" specific inhibitors for CYP3A4 and Pgp. If
you
wish to distinguish the Pgp contribution from CYP3A4 contribution, the
more
reliable method is to test the drug in Pgp -ve cell lines and then
afterwards
in transfected cells and then in CYP3A4 negative and transfected cells.
Alternatively, you may use GF120918 ( provided by Glaxosmithkline)
which to
date has shown superior inhibition of Pgp without effects on CYP3A4 at
nanomolar concentrations, (note that GF120918 inhibits other
transporters
such as BCRP). but if you are only concerned with Pgp and CYP3A4, then
this
interference should not matter ( depending whether your drug is a
substrate
for other transporters or not).
hope this helps.
Noha
Noha Nabil Salama, Ph.D.
Research Associate
DNA Sequencing and Gene Analysis Center
Department of Pharmaceutics
University of Washington School of Pharmacy
Phone: 206-616-8718
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