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The following message was posted to: PharmPK
Hello.
I have confusing to understand our rat i.v. plasma concentration data.
Plasma AUC for rat i.v. are 10.1ng*hr/mL(0.25mg/kg),
43.6ng*hr/mL(1mg/kg),
158.3ng*hr/mL(4mg/kg), then plasma clearance are constant
424mL/min/kg(0.25mg/kg), 389mL/min/kg(1mg/kg), 426mL/min/kg(4mg/kg),
respectively.
Another data indicates that this compound doesn't distribute into blood
red
cells. Then
Blood concentration is almost the half of plasma concentration and blood
clearance is almost the double
of plasma clearance.
In this situation, blood clearance exceeds the rat's cardiac
output(about
150mL/min/kg).
Does anyone have the suggestion or experience to this data?
Thank you.
Shinji Tauchi
Japan, Shizuoka, Fujieda city
tauchi_shinji.-a-.kaken.co.jp
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Shinji
Have you checked the stability of your drug in the blood and plasma in
ex vivo conditions? Is your drug metabolized by the rat plasma
esterases?
Regards,
Antoine DESLANDES, PhD
CENTELION SAS
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Dear Shinji Tauchi,
Did you check the stability of your compound in plasma?
Decay in plasma may give you very high clearance values well above
hepatic blood flow.
What is V for your compound? A high V (resulting in low plasma
concentrations) can lead to problems in recording a sufficiently large
proportion of the AUC, depending on the sensitivity of your
bioanalysis.
best regards,
Michael
Michael Gassen
Head of Pharmacology and Preclinical Development
4SC AG Fon: +49 89 700763-0 Am
Klopferspitz 19a Fax: +49 89 700763-29
82152 Martinsried E-Mail: gassen.-at-.4sc.com
Germany Internet: www.4sc.com
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The following message was posted to: PharmPK
Clearance in excess of hepatic blood flow indicates removal
mechanisms by sites other than the liver - a not uncommon finding.
Dan Sitar
Dr. Daniel Sitar
Professor and Head, Pharmacology and Therapeutics
Professor, Internal Medicine (Clinical Pharmacology)
Tel: 204-789-3532 FAX: 204-789-3932
Email: sitar.aaa.cc.umanitoba.ca
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The following message was posted to: PharmPK
Drug clearance from blood exceeding cardiac output indicates blood-flow
independent drug elimination, probably by rapid degradation or
metabolism in
the blood (plasma, RBC or endothelial cells in contact with blood). I
don't
think drug elimination by organs (e.g., liver, kidney or lung) could
lead to
this phenomenon.
Just curious, what is the Vd?
Jim J. Xiao, Ph.D.
Division of Pharmaceutics,
College of Pharmacy,
the Ohio-State University
496 w. 12th Ave, Columbus, OH43210
Phone: 614-6884328
Email: xiao.25.-a-.osu.edu
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The following message was posted to: PharmPK
Nitroglycerin and some other organic nitrates are examples of compounds
whose clearance values are larger than the total cardiac output. One
explanation for this was metabolic clearance in blood vessels.
The following references may help:
J Pharmacol Exp Ther. 1984 Feb;228(2):334-41.
Clin Pharmacokinet. 2003;42(3):205-21.
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The following message was posted to: PharmPK
Hi all
I was hoping to put together a list of the 5 top Journals in the area of
popPKPD. For the purposes of this email I would like to include both
application and methodology associated with modelling, simulation and
design
of popPKPD studies.
Part of the reason for this request is that some of the Journals that we
publish in have very low impact factors, despite being what we consider
high
quality Journals. This low impact factor is viewed by others (outside
of
our area) as reflecting poor quality work. My hope is to get objective
evidence from the experts in our area (i.e. the recipients of this
email)
about what they consider top Journals are in our field.
I would be grateful if everyone would send me a list of what they
consider
to be the top five Journals in our area (for whatever reason).
Please send this to me (not the list).
I will colate the results and post them back to the list for your
interest.
Kind regards
Steve
========================================================Stephen Duffull
School of Pharmacy, University of Queensland, Brisbane 4072, Australia
Tel
+61 7 3365 8808; Fax +61 7 3365 1688; Email: sduffull.aaa.pharmacy.uq.edu.au
www: http://www.uq.edu.au/pharmacy/sduffull/duffull.htm
DESIGN: http://www.uq.edu.au/pharmacy/sduffull/popt.htm
MCMC PK example: http://www.uq.edu.au/pharmacy/sduffull/MCMC_eg.htm
University Provider Number: 00025B
======================================================------------------------------
The following message was posted to: PharmPK
Dear all
I have underestimated the plasma clearance because very rapid
elimination
at early phase after i.v. bolus injection.
When we sampled 5min as the first sampling point, then 15min, 30min as
follows, plasma AUC was calculated 10.1ng*hr/mL(0.25mg/kg),
43.6ng*hr/mL(1mg/kg).(Case1)
When we sampled 3min as the first sampling point, then 5min, 15min as
follows, plasma AUC was 84.4*hr/mL(0.25mg/kg), 239.5ng*hr/mL(1mg/kg).
(Case2)
Extrapolated C0 values were different between Case1 and Case2.
Case1:28.18ng/mL(0.25mg/kg), 237ng/mL(1mg/kg)
Case2:2955ng/mL(0.25mg/kg), 6576ng/mL(1mg/kg)
Estimation of C0 was very important for the AUC of this compound.
In the case2, plasma clearance was 49.4(mL/min/kg) and 69.6(mL/min/kg),
0.25mg/kg and 1mg/kg, respectively then blood clearance didn't exceed
the
rat's cardiac output(about150mL/min/kg).
Thank you.
Shinji Tauchi
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