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The following message was posted to: PharmPK
Dear Colleagues,
I have two questions dealing with clearance:
I have seen people interpreting blood to plasma ratios
of greater than 1 as faster clearance of the compound
from the plasma compare to plasma. I like to discuss
theses data in terms of accumulation or association of
the compound with blood cells. Appreciate your input.
Has anyone observed transient reduce in clearance
which recovers within 24 h in normal or pregnant rats?
In one study, I have observed that AUC for last Day of
treatment is greater than the AUC for Day 1 (following
consecutive dosing for several days) but the plasma
concentrations are BQL prior to the last day of
dosing. Any comments?
Rostam
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The following message was posted to: PharmPK
Dear Rostam,
In response to:
> I have seen people interpreting blood to plasma ratios
> of greater than 1 as faster clearance of the compound
> from the plasma compare to plasma.
I understand you mean from plasma compared to blood?
> I like to discuss
> theses data in terms of accumulation or association of
> the compound with blood cells.
By definition, the rate of elimination equals CL x C (both referring to
plasma) and equals CLb x Cb (both referring to blood). So, Cb/C =
CL/CLb. If
Cb/C > 1, it can be inferred that the concentration in blood cells
exceeds
that in plasma, and this could be interpreted as accumulation in blood
cells
(most likely red blood cells, because of their abundance).
Also, plasma clearance exceeds blood clearance in this case. But I
would not
interpret this as a faster clearance. The rate of elimination, both in
terms
of amount eliminated per unit of time, or in terms of elimination rate
constant, is not affected by considering either plasma or blood. The
value
of plasma clearance is higher than blood clearance because it
interpretes
elimination driven by the plasma concentration which (in this case) is
lower
than the blood concentration. So, IMHO, the word 'faster' is misleading
here.
Please note the aforementioned consideration apply to the assumption
that
there is an instantaneous equilibrium between the concentrations in
plasma
and blood cells. If this is not the case, the blood cells would act as a
separate compartment. In that case the elimination from plasma would be
faster than from blood cells.
Best regards,
Hans Proost
Johannes H. Proost
Dept. of Pharmacokinetics and Drug Delivery
University Centre for Pharmacy
Antonius Deusinglaan 1
9713 AV Groningen, The Netherlands
Email: j.h.proost.aaa.farm.rug.nl
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The following message was posted to: PharmPK
Dear Rostam,
If po administration, it could be change in BA after repeated
administration, i.e. decrease in first pass effect.
Masaki
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[Two responses - db]
From: Rostam Namdari
Date: Fri Dec 20, 2002 12:08:56 PM US/Central
To: david.at.boomer.org
Subject: Re: PharmPK Re: Transient Reduced Clearance
Reply-To: Rostam Namdari
The following message was posted to: PharmPK
Dear Hans,
Yes, I meant from plasma compared to blood and thanks
for your thorough answer. Any comments on my second
question dealing with transient clearance issue?
Rostam
---
From: Rostam Namdari
Date: Fri Dec 20, 2002 12:12:19 PM US/Central
To: david.-at-.boomer.org
Subject: Re: PharmPK Re: Transient Reduced Clearance
Reply-To: Rostam Namdari
The following message was posted to: PharmPK
Dear Masaki,
Thanks for your response. For everyone interested in
this topic, I have to say that I am dealing with iv
injections.
Rostam
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