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The following message was posted to: PharmPK
I wonder if anyone has evaluated measuring plasma protein binding in
diluted plasma (offered by some CROs) and, if so, by what method and how
was the scaling to 100% plasma performed.
I guess that you have to take concentration of compound in relation to
protein conc into account and that it could work for albumin binding but
how does it work for compounds that bind preferentially to less abundant
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The plasma protein binding experiment at 10 % plasma is ideal method
for differentiating between highly protein bound compounds furthermore
it reduces the requirement of plasma (This is very importent
speicifically in case of mice plasma if one has to screen the series
of compounds). But, at the same time it is not suitable for highly
unbound compound. Determination of PPB at 50 % plasma is done to
differentiate between highly unbound compound where, plasma protein
binding at 100% plasma is "gold standard" as it is suitable for both
highly bound and unbound compounds and is more accurate.
Determination of PPB at 10% plasma or at 50% plasma do not work for
the copounds which binds preferentially to less abundant protein. In
such case one as to do PPB in that particular protein only for
example. AAG. The only use of PPB at 10% plasma and 50% plasma is to
differentiate between the highly bound and highly unbound compounds.
Advinus Therapeutics Pvt. Ltd.
(A TATA Enterprise)
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