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The following message was posted to: PharmPK
Dear All
On page 299 of applied biopharmaceutics and pharmacokinetics (shargel)
the following equation if appeared.
Cu = Cut
where Cu is the unbound drug concentration in the plasma and Cut is the
unbound drug concentration in the tissues in steadey state.
Do you agree with that?
Can anyone elaborate this?
Sincerely
A. Mostafavi
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The following message was posted to: PharmPK
The assumption here is that only the unbound drug is able to move across
membranes, then Cu will equal Cut. Figure 10-7 on page 147 of 'clinical
pharmacokinetics' - Malcolm Rowland and Thomas Tozer may help visualize
this concept.
However, the total drug concentrations may be different based on the
binding affinities of the drug to the tissue and plasma proteins.
Deep
Nagdeep Giri
Graduate student
Department of Pharmaceutics
University of Minnesota
612-625-2446 (lab)
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The following message was posted to: PharmPK
Dear
naagdeep
Even with the assumption that only the unbound drug is able to move
across membranes the Cu may not
be equal to Cut, however, they may be equlibrated. I think the
equlibration is different than equality. What do you think?
I wonder if equilibration between two sides of a membrane, namely
plasma and tissues, may translate to equal concentration between both
sides.
A. Mostafavi
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The following message was posted to: PharmPK
Dear Mostafavi,
Here is what i think and hope to be corrected if i am not.
>>Even with the assumption that only the unbound drug is able to move
across membranes the Cu may not
>>be equal to Cut, however, they may be equlibrated. I think the
equlibration is different than equality. What do you think?
>>I wonder if equilibration between two sides of a membrane, namely
plasma and tissues, may translate to equal concentration between both
sides.
The idea that equilibrium is different from equality should be
acceptable to most people and i agree with that. In our case here, we
are considering an equilibrated state but the equilibrium is between
the total drug concentrations in the plasma and tissue compartments and
not just between unbound concentrations in these 2 compartments. This
translates into
1) C-plasmatotal is in equilibrium with C-tissuetotal
(C - concentration)
2) C-plasmatotal may not equal to C-tissuetotal
The total concentrations in both compartments would differ if the
protien binding affinity is different in these two regions (i guess
there would not be a need to differentiate into 2 compartments
otherwise)
If we consider a simple case where the permeabilty and area of the
separating membrane is the same in both directions.
1) The permeabilty x Area product 'or' the clearance is the same in
both the directions.
2) Here the driving force for the drug to move in both the directions
would be the unbound concentrations (which of course are in equilibrium
with bound concentrations in the respective compartments)
3) There is a dynamic equilibrium between bound and unbound
concentrations in each compartment and between the compartments.
The total concentrations in the 2 comp. will not be equal but the
unbound concentrations in both the comp. should be equal (again
considering same clearance of drug in both directions)
Deep
Nagdeep Giri
Graduate student
University of Minnesota
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