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Dear Group,
I am working on a NCE belonging to high permeability class, expected to be
absorbed almost 100%. It undergoes significant first pass effect with
absolute bioavailability less than 5%. During excretion balance study of
this NCE using 14 C labeled compound, we observed that % dose excreted in
feces following an intravenous dose was almost twice as much after an equal
oral dose. The compound is excreted in Urine as well and the total recovery
in 3 days is > 90%. How can it be explained ? Thanks all in anticipation of
valuable response.
Jyoti Paliwal, Ph.D.
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Your statement that recovery is > 90% suggests you are speaking of
total radioactivity. If the amount in faeces is also total
radioactivity then you are looking at mixtures of possibly a whole
range of different compounds with different solubilities, transport
properties etc. For example, first-pass metabolism may convert most
of the material to water-soluble metabolites readily excreted in
urine. The question of why you get twice as much total C14 in faeces
after intravenous dosing therefore does not arise.
Joe Chamberlain
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