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Hi all,
I am working with a drug with 1 major metabolite. The ratio
metabolite/unchanged parent is higher in urine than in plasma (in
rats and mice). From this observation, is it correct to assume that a
renal metabolism is present? Any other hypothesis?
Many thanks,
Nathalie
[Different volume of distribution for drug and metabolite will cause
this. Also, different overall elimination rate or clearance, e.g.
because of different V, different secretion or reabsorption in the
kidney will cause this. Another mechanism could be slow formation of
the metabolite which would reduce the plasma concentration without
affecting the urine ratio - db]
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The following message was posted to: PharmPK
Nathalie:
Another explanation could be that the parent and metabolite have
different volumes of distribution.
Doug Greene
Dr. Douglas Greene
Director, Metabolism and Pharmacokinetics
GPC Biotech
101 College Road East
Princeton, NJ 08540 USA
Tel: +1 609 524-1075
Fax: +1 609 524-1050
e-mail: douglas.greene.at.gpc-biotech.com
http://www.gpc-biotech.com
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The following message was posted to: PharmPK
For renal metabolism, the renal clearance of the metabolite is lower
after
adminitration of the metabolite than after the administration of the
parent.
The M/P ratio could be higher in the urine than plasma if the parent is
not excreted in the urine but the metabolite is.
Varun
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The following message was posted to: PharmPK
Nathalie
I think it is just because the metabolite is much
polar than the parent.
Xiaodong
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dear Nathalie,
I think the metabolite has a higher ratio in urine because it is more
soluble in water(ie. more hydrophilic) than the parent drug, thus it
is excreted more rapidly in the urine. Or the pKa of the metabolite
may be different than the parent drug, increasing the excretion .
Sincerely
Guel
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