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Dear readers,
If the elimination half-life of a drug from the body is more or less a
constant
defining parameter for the drug, does the observation of much longer apparent
decay half-lives (from the plasma-concentration time profiles), following the
oral dosing compared to iv-bolus dosing (of the same dose) indicates that
there is a flip-flop kinetics present?
Does half-life need to be the same always following all routes of
administration?
Thank you for your suggestions.
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Dear,
The elimination half-life is determined by the total
clearance and the volume of distribution, i.e. t1/2 = 0.693
Vd/CLTotal. CLTotal and Vd generally are the same for different
routes of administration. So the elimination half-life is usually the
same for different routes.
If the absorption half-life (t1/2 abs) is shorter than the
elimination half-life (t1/2 el) , then the terminal portion of the
log Cp vs. t curve after per os administration will parallel the
curve after i.v. administration and in both cases reflect the
elimination half-life.
But in cases where the elimination is very rapid (ka << kel),
the terminal slope may not be parallel because the kinetics of
decline after oral administration reflects the absorption half-life
rather than the elimination half-life, which is an example of
"flip-flop" kinetics. In fact, the decline of the terminal slope may
depend greatly on how fast absorption is taking place.
Best regards,
Amir A. Tahami
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Dear Khalili:
Normally we observe Ka>Ke and by using the terminal phase of the log Cp
vs T profile we can calculate the Ke. But in cases where the Katerminal phase would be used to obtain the Ka and the initial phase will
give you the Kel. This type of kinetics is refered as flip flop
kinetics.
If you are observing longer half lives with the oral profile when
compared with the iv profile then probably you are estimating the Ke and
t1/2 from the abosrption phase (terminal Phase).
The elimination rate constant should be same irrespective of the route
of administration. Another way to confirm the flip flop kinetics would
be to find the ke from iv bolus study and compare with the rate constant
from the terminal phase of the log cp vs T oral profile. If it does not
matches with the iv profile then its a case of flip flop kinetics.
Regards,
Azher
Azher M. Hussain, Ph.D
Post Doctoral Researcher
P450 Inhibition
Xenotech, LLC
Email: ahussain.at.xenotechllc.com
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