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Dear group,
Whats the interpretation of blood to plasma concentration ratio less than 1? High binding to plasma protein binding could be one. How would it (less than 1 B/P ratio) impact on the plasma clearance (rat) values approaching hepatic blood flow? I have a compound with a B/P ratio of 0.5 and CLplasma of 50ml/min in rats.
Thanks
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If a drug does not penetrate blood cells but is restricted to the plasma, then the blood/plasma ratio is reduced to about 0.55 (1 - hematocrit). Your figure is probably within experimental error of that. You are correct to some extent about plasma protein binding but it is also important that the drug does not enter erythrocytes and that probably means low permeability. Because of the high plasma clearance, in a single dose study, the drug does not approach equilibrium with the intracellular water, lipids or proteins. This could change to nearer to B/P = 1 over a longer exposure, but it is not worth the effort when the clearance is so high.
Regards.
Ted
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The following message was posted to: PharmPK
Blood to plasma ratios allows you to convert plasma concentrations to blood concentrations, from this can determine clearance of compound in blood. Also when developing assays which one should be developed. If greater than one, use the one for blood, if less than one use the one plasma.
Stanley Cotler
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Hi Satya
Blood to plasma concentration ratio (B:P) less than 1 means the drug is not getting enough (or at all) into red blood cells and the minimum B:P is determined by the level of hematocrit in the sample that you spiked to measure B:P.
In humans, on average, the minimum B:P is 0.55. Please see the following article where the effects of B:P on clearance is briefly discussed.
http://dmd.aspetjournals.org/content/35/3/501.full.pdf+html
Regards
Masoud
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Dear all,
Could anyone please explain how blood to plasma ratio can be lesser than 1. I have an assumption that plasma is a part of Blood and concentration in plasma should always be lessthan or equal to that in blood and hence, the ratio should be 1 or greater than 1.
Thank you,
Abhijith
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The following message was posted to: PharmPK
Abhijith,
Many drugs do not enter the red blood cells (erythrocytes), which make up on
the order of 38-48% of whole blood. So the drug is only in the plasma, its
concentration in whole blood will be less. For every mL of whole blood,
there is only about 0.6 mL of plasma (assuming 40% red blood cells for round
numbers). If you have 1 ng of drug in 1 mL of blood, you have a
concentration of 1 ng/mL. But if you take out the red blood cells and
measure the concentration in plasma, then you have 1 ng of drug in only 0.6
mL of plasma, so the concentration is 1/0.6 = 1.667 ng/mL. Thus, the
blood-to-plasma concentration ratio is 1.0/1.667 = 0.6.
Best regards,
Walt Woltosz
Chairman & CEO
Simulations Plus, Inc. (NASDAQ: SLP)
42505 10th Street West
Lancaster, CA 93534-7059
U.S.A.
http://www.simulations-plus.com
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The following message was posted to: PharmPK
If the drug is highly protein bound and does not have a high affinity for the RBC;s, then B/P will be less than one
Stanley Cotler
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Hi Abhijith,
I agree with Stanley and Walt's explanation. It all depends on the affinity of drug towards particular matrix. If it has higher affinity for plasma proteins then it would be found associated more in plasma than blood which cause the ratio to be < 1.
Jigar Patel University of Alberta, Canada.
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