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Dear all,
I have to conduct a protein binding study. Previously, I used to
determine in
vitro drug protein binding. However, I learn about in vivo protein
binding
method. Is in vivo determination more reliable. If so, are there any
special
criteria (fresh plasma..) for doing such a protocol.
Thank you for your help.
Samia Ezzine
Ph.D student
Université de Montréal, Qc, Canada
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The following message was posted to: PharmPK
Though it appears a realistic measure to study protein binding in vivo
( I
assuming in Human subjects), there are quite a few practical issues.
1. Sensitivity of the analytical method, routinely you require sub
nanogram
concentrations for effectively measuring the protein binding, let us say
your drug Cmax is 100 ng/mL your drug has a protein binding of 95% then
you
are taking of free fraction is 5 ng/mL however in PB studies (by
ultrafitration) you collect something like 100 microliters so your
effective
concentration keep going down and under, top of it analytical outliers.
These analytical problems can be effectively handled by having a robust
and
super sensitive analytical methods like tracer techniques and Mass
spectrometric techniques.
My preference is to do in vivo protein binding measurements as follows.
1. Collect additional samples at around Cmax and use them for protein
binding.
2. Measure the protein binding in Human ADME study by measuring protein
binding using Hot and cold analytical methods.
3. PB measurement by equilibrium dialysis is a preferred method (though
time
taking) because this technique resolves so many practical problems.
Hope this suggestions help your study
Prasad Tata
Mallinckrodt, Inc.
St. Louis, MO 63134
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Dear All
I fully agree with Prasad. The homogeneity of population to having
fair spread or rather unspread protein binding values around a
particular mean would be almost a nonpractical in BA BE settings
Thanks and regards
Dr.Prashant
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