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The following message was posted to: PharmPK
Hi, everyone:
I am confused about terminal half life and elimination half life. Any
clarification is highly appreciated.
Sincerely,
Yan
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Terminal plasma half-life is the time required to divide the plasma
concentration by two after reaching pseudo-equilibrium, and not the
time required to eliminate half the administered dose. When the
process of absorption is not a limiting factor, half-life is a hybrid
parameter controlled by plasma clearance and extent of distribution.
In contrast, when the process of absorption is a limiting factor, the
terminal half-life reflects rate and extent of absorption and not the
elimination process (flip-flop pharmacokinetics). The terminal half-
life is especially relevant to multiple dosing regimens, because it
controls the degree of drug accumulation, concentration fluctuations
and the time taken to reach equilibrium.
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The following message was posted to: PharmPK
This review will help.
J. Vet. Pharmacol. Therap. 27,427-439, 2004
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The following message was posted to: PharmPK
Dear Yan,
>>I am confused about terminal half life and elimination half life. Any
clarification is highly appreciated.
When describing the way of a drug through the body each process such as
absorption, distribution and elimination is characterised by its own
transport process which is described in the compartment model and
associated with a rate constant. In the sum, a drug has a characteristic
profile that is determined by these different transport processes. When
talking about elimination half-life often the terminal elimination
half-life is meant. It means in simple words that all other processes
(ie those of absorption or distribution) are no longer present and
elimination entirely prevails, the change of drug over time is only
determined by the process of elimination. Elimination of course can be
the sum of different elimination processes and each of them has its own
rate constant, in those cases the term elimination half-life is broader
and would cover all of these processes, while terminal refers to the
very last one. For the determination of half-life in non-compartmental
PK analysis (a simplified model where no other rate constants are
considered) you usually take the last three measurements and make a
regression line with the best fit through these points, the slope is an
estimate for the elimination rate constant. You must be sure to have
enough data points to cover the terminal phase and not one where eg
distribution still plays a role.
Regards
Mat
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The following message was posted to: PharmPK
Dear Mat:
Thanks for your clear clarification.
One more question: if the distribution is the rate limiting step
(distribution rate constant is much smaller than elimination constant).
Then "you usually take the last three measurements and make a
regression line with the best fit through these points...", the terminal
half life (or the slope) will be an
estimate for the distribution rate constant instead of elimination
constant, is this conclusion correct? Thanks again for your help.
Sincerely,
Yan
RY80-141
PCDMPK, MRL
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The following message was posted to: PharmPK
Dear Yan,
>One more question: if the distribution is the rate limiting step
(distribution rate constant is much smaller than elimination >constant).
>Then "you usually take the last three measurements and make a
regression line with the best fit through these points...", the
>terminal half life (or the slope) will be an estimate for the
distribution rate constant instead of elimination constant, is this
>conclusion correct? Thanks again for your help.
If you still have distribution phenomena, there is still amount of drug
deposited somewhere in the body and after it has been re-distributed
from e.g. deeper into the central compartment (a transport process with
a specific rate constant), it can be eliminated; elimination is always
from the central compartment e.g. blood. Since this happens the terminal
elimination phase has not been reached, problem could be assay
sensitivity which might not allow you to cover the terminal phase
adequately and you simply might not see it or get wrong estimates. In a
dose range study you would however see that at some point previously
non-detectable areas of the profiles suddenly emerge. You can visually
evaluate this best in semi-log plots.
Regards,
Mat
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Dear Yan,
I recently also pondered this distinction and, after looking at a
couple of text books, decided that the difference is largely one of
terminology.
* Elimination half-life has a specific technical meaning in PK as
has been described by other respondents.
* Terminal half-life has no specific 'technical' definition, i.e.
terminal simply means 'the last one' (the last observable) and
therefore may, or may not correspond to the actual elimination half-
life, for reasons again described in other answers (e.g. the
analytical LLOQ means you don't detect the elimination phase).
The above seems to correspond to your point below, that the terminal
half-life could be a distribution half-life and not the elimination
half-life.
I hope I haven't confused the issue any further, and I cannot be
certain that my interpretation is correct.
Regards,
Clive
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The following message was posted to: PharmPK
Hi all
Please consider the effective half life as a better estimate of the
"half life" of your compound. This HL is very useful to estimate
accumulation after repeated administration in a linear system.
Pascal
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Hi,
Michelle Battle and I published a simple article on the concept of
effective half-life. The reference is: J Clin Pharmacol
35:763-766,1995. If you cannot readily get it, please send me an
email, and I can email it to you. Please use my clerkmaxwell.-at-.hotmail.com
address and label the subject heading " please send reprint," or it
may get inadvertently deleted. Best wishes, Harold.
Harold Boxenbaum, Ph.D.
Pharmacokinetic Consultant
Arishel Inc.
14621 Settlers Landing Way
North Potomac, MD 20878-4305
Email: harold.at.arishel.com
Website: www.arishel.com
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