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Dear All,
Is that possible to find a substance that doesnot
accumulate in body (unlike non-polar PCBs which have
high bioaccumulation) and at the same time they cannot
be metabolized in-vitro (like when added to
microsoms).
Thanks,
Ahmad
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Hello,
Years ago, I worked with the perfluorocarbon compounds in the form of
artificial blood - they were administered as an emulsion of
microspheres. They didn't accumulate in the body (except for the
tiniest bit in the liver) and definitely weren't metabolized. They
behaved like little balls of teflon (the hydrogen atoms were replaced by
the fluorine atoms - completely inert) and exhaled through the lungs,
skin and kidneys - although you might have to check on the percentage of
each route. The Green Cross in Japan supplied the emulsions to me, and
the Japanese have done quite a bit of work on the safety and efficacy
issues.
Hope this helps.
Good Luck,
Edmond Edwards, Ph.D.
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Dear Ahmad,
Gabapentin might be such a drug (not accumulating, t½ 5-7h due to renal
elimination and not metabolised, at least not in rodents and man to any
relevant extent, some metabolism in dogs).
Regards,
Dietrich
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Dear Edmond,
Thank you for your informative reply. However, I'm
looking for a substance that can be used in Reverse
phase LC , i.e. water soluble but at the same time
non-metabolizable (or poorly metabolized) by liver
microsomal incubations in-vitro.
I wonder if such a chemical ever exists?
Looking forwards,
Ahmad
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Kynurenic acid will probably work as a non-
metabolized substrate that is excreted by the kidney. It is an
end product. See Lou et al Can J Physiol Pharmacol
1994:72:161-7 and Goraksli et al JPET 1999;290:496-504.
It can be easily labelled specifically with tritium to
give a highly sensitive detection method.
D. Sitar, University of Manitoba
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The following message was posted to: PharmPK
Dear Dietrich,
Thank you for the reply, However does the fact that
(say) Gabapentin is eliminated via Kidney necessarily
mean that it cannot be metabolized by liver (say,
in-vitro incubated with liver microsomes)?
tanx again,
Ahmad
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Dear Ahmad,
Try Gabapentin.
radu
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Dear Ahmad,
Tezosentan, an endothelin antagonist formulated for iv use, is a
compound that is excreted unchanged into the bile. Metabolism in
vitro/in vivo is minimal. Of a radiolabeled dose, less than 5% was
recovered in urine and only 2-5% as metabolites in feces. The results
of the ADME studies performed with tezosentan in vitro/in vivo
(including man) will soon be published in Xenobiotica. Concentrations
of this compound in plasma and urine can be easily measured with a
LC-MS/MS method.
Regards
Paul van Giersbergen, Ph.D.
Clinical pharmacologist
Actelion Pharmaceuticals Ltd.
Gewerbestrasse 18,
4123 Allschwil
Switzerland
Telephone: ++41 61 487 3419
Fax: ++41 61 487 3490
www.actelion.com
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The following message was posted to: PharmPK
Another compound you may want to consider is Octreotide this is a
peptide
which is considered 100% renally excreted. and a half life of 1.5 hrs.
It
was a Sandoz product
Hope this helps.
Prasad Tata
Mallinckrodt, Inc.
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Another one is Metformin: It is not metabolized and about 90% of the
absorbed drug is excreted by the kidneysalong the first 24 hours.
And the other case is Lithium when it is administered as the carbonate
salt for example.
Silvia Giarcovich
Diffucap
Argentina
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