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Dear all,
I have a little doubt regarding compound's plasma protein binding and its metabolism in the presence of plasma (performed in vitro)
Assume compound's plasma protein binding is 90% so only 10% drug will be free to be metabolized in reaction mixture containing Rat Liver Microsome and rat plasma (in place of buffer)
Whether bound drug will be in equilibrium with unbound drug in this situation?
OR
this microsome will metabolise only 10% free drug not all because of the lack of equilibrium shift?
Eagerly waiting for your reply.........
Regards,
Rahul Vats
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Dear Rahul,
Protein binding always remains in equilibrium whether its in-vitro or in-vivo condition. So if 10% of the drug will bound to protein and metabolized then another fraction of drug will bound to the protein and this will contiune....
With Regards,
Dr. Tushar Nahata
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The following message was posted to: PharmPK
Dear Rahul,
> I have a little doubt regarding compound's plasma protein binding
>and its metabolism in the presence of plasma (performed in vitro)
Protein binding implies that the unbound concentration Cu is lower
than the total concentration C (fu = Cu / C). As a result, the rate of
metabolism (amounts per unit of time) will be lower, proportional to
fu.
However, eventually, all drug will be metabolized since the binding is
a dynamic equilibrium. If Cu is reduced due to metabolism, some drug
is released from the protein binding sites. At any time fu = Cu / C
will remain constant (only for very high concentrations fu becomes
dependent on C, as a result of the limited number of binding sites).
best regards,
Hans Proost
Johannes H. Proost
Dept. of Pharmacokinetics, Toxicology and Targeting
University Centre for Pharmacy
Antonius Deusinglaan 1
9713 AV Groningen, The Netherlands
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The following message was posted to: PharmPK
Dear Rahul/Dr. Tushar,
Yes thats true, but it depends on individual because the protein content
is different with different individual. And if the available protein
is less then binding will differ and more fraction of unbound drug
will be seen.
I hope you got my point.
Regards,
Aslam Burhan
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The following message was posted to: PharmPK
If your extraction procedure is same as in plasma, you need a partial validation, otherwise full validation. Recovery change with matrix, hence need to check for LOQ also.
Regards,
S.Basu
Senior Research Scientist
Sai Advantium Pharma Ltd, Pune
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