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0:00
Welcome to this short
lecture on metabolism,
excretion, and the
therapeutic window.
I'm Karel Allegaert,
clinical pharmacologist
working at KU Leuven.
0:14
Why are we discussing
this topic?
It is because four
parameters are
the determinants of
concentration/time
profiles: absorption,
distribution, metabolism,
and excretion.
For information related to
absorption or distribution,
I refer to another lecture.
While in this lecture
we'll focus on
metabolism and excretion as both
are determinants of the
subsequent clearance
or elimination of
a given compound.
0:47
What is the definition
of clearance?
While in the most common setting
which means
first-order kinetics,
linear kinetics, it is the
amount of blood cleared,
so it's a volume, from the
drug in a unit of time.
This unit can be
seconds, minutes,
or hours depending
on the pattern.
While in zero-order kinetics
which means that it's
commonly in toxic or
intoxication type of settings,
things become non-linear
and then it's the amount
of drug cleared in
a unit of time.
The most common example
is ethanol as this will
shift quite fast from linear
to non-linear kinetics.
1:31
What is the practical
use of clearance?
It has to do with the
dose required to achieve
target plasma concentration and
obviously subsequent
effect at steady state.
I hereby use an
illustration using
continuous intravenous
administration of
two potential drugs.
Drug A cleared five
liters per hour,
and Drug B cleared
10 liters per hour.
If you would have
the same dose rate,
clearance will result in the
steady state concentration
and as Drug A has a lower
clearance compared to Drug B,
Drug A will have a higher
steady-state compared to
Drug B or the other way around
because Drug B is
cleared faster,
the steady-state
concentration will be lower.
Obviously, if you would
like to attain the
same concentrations,
you could still
adapt the dose rate
but at least it does illustrate
the link between the dose needed
and the clearance as present.
