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Dear all,
As per the definition, Half life is independent of the
concentration in first order reaction. So my doubt regarding this is,
while calculating PK parameters by NCA we are considering the
elimination as first order reaction. But why does the half life vary
depending upon the time points we select for calculating the Kel,
Shouldnt it remain the same irrespective of time points what ever we
select for Kel? Please let me know if there is any globally accepted
criteria, as if how to select the time points in elimination phase.
Thanks in advance,
With regards,
Vijaya Bhaskar,
GVK BIO.
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Dear Vijaya,
For the calculation of half life you have to select those points which is present in true elimination phase means phase where absorption is completely over and so decrease in plasma concentration is because of elimination only (no distribution and absorption phase is involved).
In case when you are selecting those points where absorption phase has not been completed then it will change the half life value as absorption is concentration dependent.
There is no strict guideline but we usually select last 3-4 points after I.V administration which gives me are value >.99.
Regards,
Rahul Vats
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Vijaya,
Your question brings up a much larger issue in PK in general - the tail wags the dog. Instead of asking "how to calculate the half-life?" we should ask first - "does half-life exist?" We have come to consider half-life as a given, whereas in reality it is nothing but a model parameter, and therefore does not "have to" exist at all (unlike clearance and volume of distribution, for example). We tend to say a priori "let's calculate the half-life", then we bend all other parameters - and, more importantly, our understanding of actual PK processes, fitting the reality to the model, instead of the other way around - to fit the concept of "mandatory" half-life. That is also how utterly misleading and meaningless values of V-beta come to being. In case of a non-compartmental analysis, what is wrong with saying something like "95% of the drug was eliminated after 5 h, and 98% after 10 h"?
Andrew Volosov
Shire HGT
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