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Dear All,
Greetings. I am here posting a query in the basics.
I have come across the terms "Alpha & Beta half lives", while
searching the terminal elimination half life for a drug. What exactly
they are?
In which case, we consider those half lives, instead of terminal
elimination half life.
I would be much grateful, if any one kindly reply with details.
Thanking you in anticipation,
Habeeb Ibrahim
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The following message was posted to: PharmPK
Dear Habeeb,
When carrying out a "non-compartmental" PK analysis, one estimates an
apparent terminal half-life from a subjective assessment of the
concentration-time profile during an apparent mono-exponential phase. An
estimate of an apparent terminal half-life is determined,
irrespective of
the number of potential exponential phases.
If one fits a sum of exponentials to the data the best model may be
considered to be, for example, a bi-exponential function. In this
case, the
model will generate two half-lives associated with the bi-exponential
function; these may be called the alpha and beta half-lives. The
elimination
half-life will be a hybrid of (i.e. somewhere between) these values. The
elimination half-life can be derived from the fitted model. The beta
half-life will more closely reflect the terminal half-life.
The alpha and beta half-lives are likely to be predominately
associated with
distribution and elimination, respectively.
Regards,
Charlie
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Dear Habeeb
Alpha is half-life for distribution phase. Beta is half-life for the
elimination phase. Gamma for the terminal phases. The useful half-
life is an overall elimination half-life calculated from
noncompartmental pharmacokinetics.
Thank you for your help. it is really appreciated
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Dear Ibrahim,
By convention, alpha is Distribution and Beta for Terminal Halflife.
Santosh Tata
Bioanalytical Division, BEC
Apotex Inc, Bangalore
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Dear Ibrahim
Alpha and beta elimination half lives are calculated if you are
trying to calculate the pharmacokinetic parameters through
compartmental analysis.
If the compound you are working on fits into 2 compartment model then
you have alpha and beta as their distribution and elimination rate
constants and alpha and beta half lives as their corresponding half
lives.
Beta half life is the over all elimination half life of the compound.
While if you calculate the pharmacokinetic parameters through non
compartmental analysis you will have overall elimination half life
and no nomenclature as alpha and beta half lives
Hope this helps
Pavan
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The following message was posted to: PharmPK
Dear Pavan,
The terminal half-life estimated by non-compartmental analysis will be
equivalent to the "overall" or effective elimination half-life only
for a
one-comparment model.
The effective elimination half-life (i.e. the half-life that
contributes to
the overall accumulation of drug) can be estimated, by definition,
from the
observed extent of accumulation after repeated doisng at steady state
and
the dosing interval.
Regards,
Charlie
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Dear Charlie
Point well taken, but as far as the compound follows first order
pharmacokinetics, the elimination half life when calculated after
multiple dosing will be same as on single dose, whether the compound
follows one compartment or multiple compartment model.
Regards
Pavan
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The following message was posted to: PharmPK
Dear Pavan,
You are correct that the elimination half-life will be identical after
single and repeated dosing according to linear kinetic theory,
irrespective
of the model. My point is that one cannot estimate elimination half-life
from single dose data alone for a multiple compartment system using a
non-compartmental approach. The calculated terminal half-life will
overestimate the elimination half-life to some extent.
Charlie
[Charlie, how do you calculate terminal half-life using a non-
compartmental approach? - db]
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The following message was posted to: PharmPK
David,
Ok, perhaps we should say "apparent terminal half-life". For a true
two-compartment model, the terminal half-life will be similar to the
beta
half-life in this argument. The point I'm trying to make is that the
beta
half-life does not correspond to the elimination half-life which will
be a
hybrid of the alpha and beta half-lives.
Charlie
[Right, the beta half-life and the k10 half-life are different
parameters, however, for a two-compartment model the beta half-life
is the terminal half-life from the non compartment approach - db]
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