Many patients exhibit reduced
efficacy to medicinal treatments over time. Some
of this can be attributed to over-expression of
efflux pumps. Thus, understanding the affinity
and concentration dependence of drug efflux allows
us to understand how significant this process
is in potential relapses to susceptible drugs.
In our group, drugs are assessed for changes in
transport rates through an in vitro human derived
Caco-2 cell monolayer system to establish relative
affinities for the P-gp (MDR1) efflux protein
responsible for removing these drugs from cells.
Evaluating the significance of (or lack of) P-gp
mediated efflux in the transport of anti-epileptic
drugs, antihistamines and novel antimalarial compounds
are currently underway. Although epithelial in
nature, Caco-2 cells have tight junctions more
closely resembling the blood brain barrier, and
when taken in context, can provide some insight
into P-gp mediated mechanisms at this barrier,
as well as indicating the likelihood of quite
variable bioavailability.
In addition, with some areas such as digoxin
transport, we are able to explore metabolite transport
rates, allowing us to gain a more complete picture
of P-gp involvement for drugs as they are degraded.
A third stream of this in vitro work involves
examining the role of P-gp inhibition on transport
of substrates. One current project involves examining
the role of macrolide antibiotics on digoxin transport,
which can provide further insights into a range
of potential drug interactions.
Contact Details of Program Leader
Name: Dr Andrew Crowe
Institution: WABRI - Curtin University
Phone: +61 8 9266 3423
Fax: +61 8 9266 2769
Email:
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