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Dear All,
There is a question that whether one compound given through IV bolus will
encounter enterohepatic circulation in the body or not. If so, why "hump(s)" in
an exposure profile are really rare for IV bolus administration?
Any comments on this topic are highly appreciated.
Thanks in advance,
MJ
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The excretion into the bile is a function of the concentration that
comes in contact with the basolateral membrane of the hepatocytes, that
is the side of the liver in contact with the systemic circulation.
Giving the drug iv, allows the drug to distribute in the volume of
distribution and the systemic concentration in significantly lower than
the concentration in the hepatic portal blood when an oral drug is
absorbed and comes in contact with the basolateral side of the liver
before distribution into the volume of distribution.
Leslie Z. Benet, Ph.D.
Professor
Department of Bioengineering & Therapeutic Sciences
Schools of Pharmacy & Medicine
University of California San Francisco
533 Parnassus Avenue, Room U-68
San Francisco,
CA 94143-0912
Email: leslie.benet.-at-.ucsf.edu
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Dear MJ
The answer to your question is yes excretion into the bile and as a
result enterohepatic circulation (EHC) can happen for both oral and iv
dosing regimens. However as you stated humps in iv dosing is rarely
reported.
Perhaps this begs a more fundamental question as based on what "hard
evidence" we often associate humps (in particular comparable to the
first Cmax) to EHC?
To be able to see a significant second hump in plasma concentration a
drug should have reasonably high fa and Fg values, a high hepatocyte
concentration as well as high affinity to apical (canalicular) efflux
pumps of the hepatocyte. EHC also depends on the gallbladder emptying
and interdigestive migrating motor complex processes but as far as we
know these are smooth processes that don't seem to be able to explain
humps.
Any thoughts/comments would be greatly appreciated.
Regards
Masoud
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I suspect that the IV route was chosen for drugs often, though not
exclusively, due to their poor absorption/bioavailability, thus making
it very rare to note EHR after IV administration
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I agree with Zuyu opinion. If the drug is less liposoluble has
difficulty to get the biliar duct to reset the EHR and increase half
life and bioavailability. That was said IV administration is chosen to
improve plasma concentration and avoid hepatic first pass. Regards
Professor Pedro Saul Lipszyc MD
Clinical Pharmacologist
Chairman
Department of Pharmacology
University of Buenos Aires Medical School
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