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To the PharmPK group,
I had an interesting result in the bioavailability studies of a NCE.
BA was 95% in bile duct ligated rats and 10% in normal rats.
Bile had strong affect on absorption.
Do you know any other cases like this and reason for decreased BA?
Thank for your help
M.Ishii
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Hello
Complexation in the presence of bile salts is a possibility. You can
check it by in situ absorption studies with bile and without bile. You
can add bile in the reservoir and recirculate in the various regions of
intestine along with your NCE. There are few papers reporting this
phenomenon and have been published in Pharmaceutical Research.
Hope this helps.
Atul
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Ishi,
Bile duct ligation cause downregulation of MRP2 (cMOAT), an efflux protein
responsible for biliary excretion. Perhaps your drug is a MRP2 substrate.
Overcoming MRP2 efflux will result increased gastrointestinal absorption
causing higher bioavailability. This may be a possible explanation.
Cheers for now,
Abhijit
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Ishi:
I agree with Abhijit's comments for probable reasons for enhanced
absorption following bile duct ligation. Few references available to
study this effect. Please check references on CPT-11 & SN-38
(camptothecin analogs) and role of cMOAT. I presume mol.wt of your
compound may be > 500.
Srinivas Mamidi
Dr.Reddy's Research Foundation
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The following message was posted to: PharmPK
Thank you for your comments.
But, our NCE was excreted mainly via urine in rat i.v. study (more than
90%),
and mol.wt of this compound is nearly 400.
It became clear that most was excreted by glomerulus filtration in the later
study.
So, I expect reason for decreased BA was interaction with bile componets.
May I push forward development of this compound, if expectation is right ?
Will there be the example that such a compound became product at the past ?
Please advise me.
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