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The following message was posted to: PharmPK
Dear pharmacologists who read this,
I have been desperately searching for the definition of "apparent
half-life", but to no avail. It seems to be the one kind of half-life
that almost everybody refers to as casually as anything, but no one
bothers to define.
In your list archive, I have found a clue that the issue may have been
discussed before here (in 1999). Although I was unable to unearth this
discussion, I concluded that if anywhere, it could be on this list
that I would find the answer ...
What I need to know is of a general nature, yet entirely pragmatic,
and I'll phrase the question in several ways:
When a pharmacologist says "apparent half-life", what do they mean? In
what way does "apparent" qualify "half-life", i.e. what kind of
information does it add? What distinguishes "apparent half-life" from
"half-life" (in meaning)? What do you make clear by saying "apparent"?
I would be truly thankful for any feedback on this.
Best regards,
Florian v. Savigny
--
Florian v. Savigny
Medizinische Uebersetzungen
Medical Translations
--
mail.-at-.fsavigny.de
www.fsavigny.de
August-Bebel-Str. 126
33602 Bielefeld
Germany
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Florian,
I dont know of any well accepted used of apparent half-life. However
it is used in a pragmatic way to talk about the half-life that would
explain the time to eliminate most of the amount in the body or to
almost reach steady state. This can be helpful when the elimination
(and accumulation) processes are described by complex models such as
those with multiple exponentials.
There is no simple 'half-life' that can be derived from multi-
exponential models to predict when most of the drug is eliminated or
most of the time to steady state has passed. However, many people are
familiar with this concept when applied to simple one compartent first
order elimination systems so it makes it easier to simplify the
complexity of a multiple exponential model by making up an apparent
half-life that is derived from 1/4 of the time to 90% steady state or
1/4 the time to eliminate 90% of the drug. If the disposition model
was really a simple one compartment first-order model then the half-
life would have this property.
It was popular for a while among anaesthetists to describe multi-
exponential disposition with a 'context sensitive' half-life. This had
a similar sort of 'apparent half-life' flavour but was complicated
further by trying to describe the half-life for loss of half of the
effect. Even more of an approximation to the model used to describe
real obervations.
The bottom line is there are no free lunches. If you are prepared to
accept some kind of approximation to the best available description of
the time course of concentration (or even drug effect) then an
apparent half-life may have some use to quickly express the ball park
behaviour of a drug -- but you have to give up accuracy of the
prediction in exchange for the simplicity.
Nick
--
Nick Holford, Dept Pharmacology & Clinical Pharmacology
University of Auckland, 85 Park Rd, Private Bag 92019, Auckland, New
Zealand
n.holford.aaa.auckland.ac.nz
www.health.auckland.ac.nz/pharmacology/staff/nholford
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The following message was posted to: PharmPK
Hi Nick,
I am more familiar with the term "effective half-life" to describe the
half-life consistent with extent of accumulation and time to steady
state
(see: Boxenbaum H, Battle M. Effective half-life in clinical
pharmacology.
J Clin. Pharmacol. 1995; 35: 763-766).
My experience with "apparent half-life" is in terms of an "apparent
terminal
half-life" in non-compartmental analysis (this parameter is almost
always
described as such in toxicokinetic analyses). In this case, the term
"apparent" is used to emphasise that the true terminal phase may not
have
been characterised due to e.g. assay limitations.
Best Regards,
Charlie
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The following message was posted to: PharmPK
I learned the concept of "effective half-life" (te) from a workshop by
Dr. Gabrielsson. It is defined as
te=ln2*Vss/CL or te=ln2*AUMC/AUC. I guess "apparent half-life" is just
another name.
I wonder under what situations we might need it. Appreciate more
comments.
Jun Shen
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The following message was posted to: PharmPK
Dear Jun Shen,
My understanding of the term "apparent" elimination half-life is
that it is specifically used in Non-compartmental analysis since the
assumptions made mean that this cannot be assumed to be same as that
obtained from compartmental modelling e.g. the K10 half-life (halflife
of the rate at which the drug leaves the system from the central
compartment)
The apparent elimination halflife from NCA may be similar but as
it is often a composite function that including other elements e.g.
distribution etc. the caveat "apparent" is added, much like you will
sometimes see a volume expressed as V/F from extra vascular models;
because the fraction of dose absorbed (F) cannot be estimated.
Best regards,
Simon.
--
Simon Davis
Senior Scientific Consultant
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If we were to collapse a multi-compartment model to a one compartment
model the apparent or effective half life would be what we use for
multiple dosing. The limitation is that not all drugs can be
collapsed. For
All dosage regimen equations strictly apply only when,
(beta/k10) * (1 + (k12/k21)) is approximately 1
e.g. the equation has the value of
0.947 for digoxin
0.990 for warfarin
0.846 for cephalexin
This is why, despite the fact that an open two-compartment model is
the better description of the pharmacokinetics of these drugs, a
simple one compartment model may often be assumed for dosage regimen
purposes.
In some cases, e.g. Vancomycin, because Vanco has such a large
therapeutic range, the peaks are virtually ignored by clinicians and
the troughs are calculated using the terminal elimination rate
constant obtained after distribution is complete (usually taken an
hour after termination of the infusion during the fourth dose.)
Michael C. Makoid, Ph.D.
Professor, Department of Pharmacy Sciences
School of Pharmacy and Health Professions
Professor, Department of Pharmacology
School of Medicine
Creighton University
2500 California Plaza
Omaha, NE, 68178
[Hopefully I redrew the equation correctly - db]
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The following message was posted to: PharmPK
It may also refer colloquially to a situation where there is flip-flop
kinetics i.e. absorption takes much longer than elimination so the
half-life that appears to be reflecting elimination really reflects
absorption. A examples is with long acting intramuscular injections.
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Jun Shen,
Effective half-life is calculated from the accumulation of the drug in
the body whenever the estimation of half-life is not accurate. There
are not same.
Thanks
Ayyappa
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The following message was posted to: PharmPK
Hi,
I am not sure why the discussion on "apparent half-life" has moved
toward "effective half-life". To me, apparent half-life refers to an
estimated half-life influenced by other factors than the elimination. If
you have a sustained release formulation, e.g., and the half-life you
measure is longer than that after an iv dose of the compound, you are
obviously estimating the apparent half-life. The properties of the
formulation affect the observations to the degree that the "true"
parameter cannot be estimated. Another example would be the apparent
clearance of a compound after an oral dose: the estimated clearance is
influenced by bioavailability and might not reflect the true clearance,
i.e. one estimated after an iv dose.
Toufigh Gordi
Toufigh Gordi, Ph.D.
Associate Director, Pharmacokinetics
Depomed, Inc
1360 O'Brien Drive, Menlo Park, CA 94025
tgordi.at.Depomedinc.com
http://www.depomedinc.com
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The following message was posted to: PharmPK
Dear Michael,
You presented the following equation:
> All dosage regimen equations strictly apply only when,
>
> (beta/k10) * (1 + (k12/k21)) is approximately 1
Please note that this expression is equal to:
Vss / Vbeta
since Vss = V1*(1+k12/k21), Vbeta = CL/beta, and k10 = CL/V1.
So, if Vss is close to Vbeta, the two-compartment model can be
replaced by the one-compartment model for purposes like dosage
calculations.
best regards,
Hans Proost
Johannes H. Proost
Dept. of Pharmacokinetics and Drug Delivery
University Centre for Pharmacy
Antonius Deusinglaan 1
9713 AV Groningen, The Netherlands
Email: j.h.proost.aaa.rug.nl
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