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Dear Group,
I would highly appreciate if anyone from this group let me know the
theoretical residual blood volumes in each tissue (Viz., Liver,
Pancreas, brain, Kidney, Spleen, Lungs etc.,) in mouse and rat in
order to apply the correction factor for tissue distribution studies,
when it's not feasible to remove the blood completely from the organs
by perfusion.
Thanks in advance.
Regards,
Syed
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The following message was posted to: PharmPK
Dear Mustafa,
I would welcome suggestions from the group if my premise be
unconvincing.
Do you agree that the blood contained in the organ is the circulating
blood?
And the circulating concentration of the drug or New Chemical Entity
(NCA) is likely to be same in blood contained in all the tissues (note
that this is not the NCA distributed into the tissue which is different
altogether).
Now, when you homogenise the tissue with the blood volume that the
tissue would normally contain, and finally substract the circulating
concentratrion, don't you think it would result in reasonable estimation
of the tissue distribution.
Once again I would welcome experts in the group to suggest further,
Hope this discussion would be encouraging and interesting,
Cheers,
Jagannath
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The following message was posted to: PharmPK
Dear Jagan/Mustafa,
To enable such correction, knowledge of vascular blood volume is also
essential in addition to knowing the blood concentration of the analyte
of interest and I think that's what Mustafa is interested in. Knowing
the concentration and the blood volume, one could then calculate the
mass of analyte present in the vascular space (blood) which when
deducted from total mass present (tissue + blood) gives analyte mass in
the tissue.
Coming to the original question by Mustafa - I do not know if vascular
volumes for different tissues/organs of mouse and rat already exist in
the literature, but one can estimate easily by using tissue impermeable
(vascular volume) markers such as Inulin. Following IV administration of
radiolabeled marker (say 14C-Inulin), collect a blood sample (at about 5
min post-dose) and immediately sacrifice the animal to harvest the
tissues of interest. Measure the radioactivity in the blood as well as
tissues following appropriate digestion of the samples. Knowing
radioactive concentration (b; dpm/ml) in the blood and total
radioactivity in tissue (a; dpm), volume of blood present (a/b; ml)
could be obtained which can then be normalised by the tissue weight
(ml/g).
Hope this helps.
Kasiram.
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For one consistent set of values for the blood remaining in tissues
after bleeding in the rat, see Table II in the paper by Bernareggi
and Rowland, J. Pharmacokinetics and Biopharmacokinetics, v19: 21,
1991.
David Levitt,
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Dear Mr.Mustafa,
Bit a old reference, but may be of some use to you
Journal of Pharmaceutical Sciences; (74) 1007-1009; published in 1985
Regards,
J Martin Gnanamuthu
Dept of Drug Metabolism and Pharmacokinetics,
Orchid Research Laboratories Ltd,
Chennai-119
India
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The following message was posted to: PharmPK
Here is another reference for volume fraction of blood in organs and
tissues
of mouse, rat, dog and human (Table 30):
Brown, RP., et al. "Physiological Parameter Values for
Physiologically Based
Pharmacokinetic Models". Toxicology and Industrial Health, Vol 13,
No. 4,
1997, p. 407-484.
---
Christopher J. Endres
Department of Pharmaceutics
University of Washington
Seattle, WA 98195-7610
Office: Health Sciences Building, H-279A
Telephone: (206) 685-0902
E-mail: plank.-a-.u.washington.edu
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