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Does anyone have any precedents for a compound to undergo enterohepatic cycling but no parent or
metabolites in feces.
So, a compound that undergoes complete reabsorption after biliary elimination and systemic
metabolism to metabolites that are renally eliminated.
Thanks,
Charlie
Charlie Brindley PhD
Larchwood
Shieldhill Road
Quothquan
Lanarks ML12 6NA
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Hi Charlie,
Bile acids? almost 95 % are reported to be reabsorbed ...with 5 % daily
loss via feces ...
Regards
Sagnik
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Thanks Sagnik, this does suggest that an administered compound could, theoretically be completely
re-cycled without fecal recovery?
Charlie
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Yes, may be if they have structural similarity (cholesterol like structures)...
Interesting thing would be to see, which transporters are they using..as not a lot of examples are
there of drugs that employ bile acid transporters for their disposition...
Regards
Sagnik
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Hi, Charlie.
How do you prove that you had an enterhepatic recirculation?
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Hi Lee,
May be from the hump in plasma-time curve..a guess :-p
Regards
Sagnik
[Cannulated bile duct might be one part of the puzzle - db]
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Hi All,
Bile-duct cannulated study has not been performed. The compound has appropriate characteristics (MW
of 400 and polar) but not recovered in faeces and secondary peaks not observed at meal times.
So, jury is out I think?
Charlie
Charlie Brindley
--
Dear Sagnik
This "HUMP" or Secondary peak could also be because of differential absorption of the drug in lower
intestine :)
Commonly observed phenomenon for Simvastatin and Diclofenac and many other drugs which do not go
hepatic recirculation (hope I have quoted the right examples)
I agree with David that cannulated bile duct might be useful tool along with estimation of
Glucuronide metabolite.
Warm Regards
Bhupesh
Bhupesh Pratap
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Hi, Sagnik.
The hump can be from other reasons.
Also BDC only can tell you about the billiary excretion not absorption after.
Two animals connected each other through the bile ducts needed (2014 DDT paper).
Wheeseong
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Hi Charlie,
Just a question: You have neither conducted the bile-duct cannulated study, nor seen the secondary
peaks; then how can you be sure of enterohepatic circulation?
Does this compound form glucuronides? Is it a substrate of basolateral efflux transporters (Mrp3/4).
I agree with Bhupesh that only from secondary peaks you can not be sure of enterohepatic circulation
and thanks for the examples.
Kind Regards
Sagnik
Sagnik Chatterjee
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Hi All responders,
I seem to have caused some confusion, so please let me clarify:
Multiple peaks are apparent in the plasma profile of healthy humans after intravenous dosing; around
2 h to 6 h post-dose.
The compound is a good candidate for EHC (MW 400 and polar); however, not known if excreted in bile.
Furthermore,
No parent drug in faeces - most compelling evidence for no EHC?
No secondary peaks in rats or monkeys
Peaks do not occur at mealtime (4 h post-dose).
Which brings me to my original query; are there any precedents for drugs known to undergo EHC but
not seen in faeces?
I realise there are alternative mechanisms for the secondary peaks; e.g., binding to blood or tissue
components and re-distribution into plasma.
Thanks,
Charlie
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