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Dear colleagues,
Can there be differences in PK parameters when one conducts whole blood PK instead of plasma PK?
Regards,
ThomasApy
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Thomas,
There will be numerical differences between whole blood pharmacokinetic parameters and plasma pharmacokinetic parameters. This occurs because you are measuring the drug levels in two distinct, but related, biological matrices. It is relatively easy to convert between the two, and neither matrix is "better" than the others. I wrote about whole blood and plasma in a blog post recently. You can read it here: http://wp.me/p1fZzZ-6D. The main Learn PK/PD blog page is located at blog.learnpkpd.com.
I hope that helps. Best regards,
Nathan Teuscher
PK/PD Associates
www.learnpkpd.com
Nathan Teuscher
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Dear Thomas,
This may depends on the drug binding with erythrocytes and other cellular matter in the blood.
Dr Zafar
"Prof. Dr. Zafar Iqbal"
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There will be a big difference in the concentration of the drug in blood and plasma if there is a substantial uptake of the drug in the erythrocytes. The concentration of the drug will be several fold greater than in plasma (egg, cyclotron, chlordane). The best thing is to determine blood/plasma concentration ratio at wide concentration range and see if this ratio remains constant or not. If it remains constant then it does not matter if the drug concentration is determined in plasma or blood since the concentration from one matrix will give the concentration in the other matrix. If the ratio is not constant then you are dealing with non-linear uptake of the drug in erythrocytes and we have a much complex situation.One would then have to determine drug concentration in the blood.
Hope this helps.
Aziz Karim, BPharm, PhD,FCP, ABCP
AzK Consulting Inc.
azia_karim.-a-.yahoo.com
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The following message was posted to: PharmPK
Hi Thomas,
There can be differences between blood and plasma PK. It will depend on the characteristic of your drug. If your drug accumulates in blood cells, then you would see higher exposures in blood. E.g. in case of antimalarials which have high blood to plasma ratio, you will see high blood concentrations as against plasma. So first thing you can do is to do a blood to plasma partitioning study in vivo or in situ. Based on these results, you can decide whether to do plasma or blood PK.
Hope it helps.
Best Tausif
Tausif Ahmed, Ph.D.
Associate Director, DMPK and Toxicology,
Sai Advantium Pharma Ltd., Building 1, Plot No. 2, Chrysalis Enclave, International Biotech Park,
Phase II, Hinjewadi, Pune - 411 057,
Maharashtra, India
"Tausif Ahmed (Dr.)"
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The following message was posted to: PharmPK
yes, that depends on the target and the type of compounds you are
screening. It also depends on blood to plasma ratio of the compounds
under test.
vijaya bhargava
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The following message was posted to: PharmPK
If you take care to lyse platelets and cells!
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Or if the drug targets receptors on white cells or is taken up and
stored by platelets. Getting an idea of whole blood conncetration is
not a trivial pursuit.
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A practical difference that I would think off in regard to the difference between plasma and whole blood pharmacokinetic parameters is in respect to the AUC, clearance and vloume of distribution. These values are usually fairly close between the two matrixes except when the drug is highly partitioning into red blood cells. In this case plasma PK values can be misleading, especially if the whole blood wasn't collected for comparison and in asbense of in vitro RBC partitioning values. In vivo high RBC partitioning will lead to low plasma AUC, high plasma clearance, and high plama volume of distribution values. The high clearance values may cause in vitro-in vivo discorrelation, especially if the drug has low intrinsic clearance values. As you can imagine. this can creat a delima and extensive resourses to pinpoint the causes of the in vitro-in vivo discorrelation.
My recommendation is to either use whole blood for your PK measurement or you can use plasma with precuasion. If you notice any issues with the plasma PK data you'll need to check the plasma stability and the RBC partitioning for your compound. Having said that, from my experience using plasma or whole blood PK calculations most of the time won't creat any discrepancy.
Hope this helps,
Best regards,
Mohammad
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The following message was posted to: PharmPK
Dear Thomas,
The following article would probably be of interest to you: The AAPS Journal, Vol. 12, No. 3, September 2010, p290-293. The article deals with the use of DBS (dried blood spot), which is gaining interest, and PK issues arising from this new approach, as such it essentially deals with PK in blood vs plasma.
Patrice Larger
ROTTAPHARM | MADAUS
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