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The following message was posted to: PharmPK
Dear readers,
In the cases of enterohepatic recirculation as manifested in the
presence of second hump in the blood concentration-time curves, how
should one measure elimination half-life, ie. which line's slope should
be considered?
Any suggestions would be greatly appreciated.
[Interesting question - I would try to set-up a suitable compartmental
model with a delayed bile emptying - see
http://www.boomer.org/manual/EG/ehrc0/ehrc.html for a model and Boomer
.BAT files (this must have been a question asked earlier ;-) - db]
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The following message was posted to: PharmPK
Dear Panteha
>In the cases of enterohepatic recirculation as manifested in the
presence of second hump in the blood concentration-time curves, how
should one measure elimination half-life, ie. which line's slope should
be considered?
I am analysing data that seems to display enterohepatic circulation at
the moment. Basically the only way you can compute 'half-life' is from
the compartment model - so you will have to model it. The model shown by
David Bourne (http://www.boomer.org/manual/EG/ehrc0/ehrc.html) is the
usual setup - although I suspect 'kg' and 'k_empty' would not be
globally identifiable since the RLS would be the gallbladder emptying
delay (is this your understanding David?). You can however estimate the
fraction of drug that undergoes enterohepatic recirculation and the
delay in gallbladder emptying.
The big question - however - is why you would want to know half-life?
Regards
Steve
Stephen Duffull
School of Pharmacy
University of Queensland
Brisbane 4072
Australia
http://www.uq.edu.au/pharmacy/duffull.htm
[Yes, Steve I think we are on the same page. I would be inclined to set
k_empty to some arbitrarily high (fixed) number and adjust emptying
time. If you have some information about amount excreted versus the
metabolism steps kg shouldn't be too much of a problem. Identifiability
could be a challenge with just plasma data. I wonder if the relative
peak sizes would give enough information to determine ke and kg - this
would be related to the fraction term Steve has above. k_empty is always
going to be tough if you want ka. Maybe I need to do a 'sensitivity'
analysis with a .BAT file - db]
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The following message was posted to: PharmPK
I completely agree with Dr. Aarons. To do a precise modelng for a drug
with significant EHC, you may have to evalaute the drug concentration
vs. time profile in bile in addition to the blood drug
concentration-time profile. If you are only interestd in evaluating the
drug disposition, mean residence time (MRT) in the body rather than
elimination half-life would give you a better idea, becasue this
parameter is a statistical parameter that characterizes the "shape" of
the drug concentration-time profile.
Yan-Ling HE, Ph.D
Department of Anesthesia
MGH, HMS
e-mail: yhe.at.Bics.bwh.harvard.edu
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