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Dear all, We have done Caco-2 assay for one of our compound along with
Digoxin standard.the efflux ratio for digoxin is within the limits
according to FDA. The efflux ratio for our compound is 6. How do we
consider whether the compound it is P-gp substrate or not. I think it
might be because of other transporters also. How to determine this?.
please help me regarding this. Thanks & regards, Sekhar
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Hi Sekhar,
Your efflux ratio suggests it to be a mild to moderate p gp substrate
to confirm it check for the transport of the drug from B-A
(Basolateral to apical) in the presence of P gp inhibitorif there is a
high percent of inhibition in the transport of drug from B-A in
presence of inhibitor compared to the transport of drug in absence of
inhibitor it confirms to be a Pgp substrate. Further if you want to
check there are commercial kits available for determination of IC 50
for Pgp. The in vivo approach of confirming is to compare the
bioavailability of drug in normal and -mdr1 knockout mice (these are
very costly and not available in India) or in -mice dosed with Pgp
inhibitor.All the best
--Naveed Shaik Abdul
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