0:00
Hi, my name is Jarkko Rautio.
I'm a Professor in
Pharmaceutical Chemistry
and Vice Head at the
School of Pharmacy,
University of Eastern Finland.
The focus of this lecture
is on prodrug strategies
to overcome problems
in drug therapy.
0:18
This slide shows you an
outline of the lecture.
The first part will briefly
cover the broad concept
of what prodrugs are and
what prodrugs there are.
This will then lead to
examples of prodrugs that
have been able to overcome
various ADMET issues.
Most of the examples
will be dealing with
prodrugs that were
made to improve
either poor solubility
or poor lipophilicity.
But there'll also be
examples designed to reduce
toxicity issues mainly by
controlling the release
of the active parent drug.
I will then discuss
some prodrug numbers
and recent prodrug approvals.
The final part of the
lecture will shortly
cover preclinical issues
regarding prodrugs,
and things to consider
when working on prodrugs
with a take home message.
Several examples given in
this lecture are described
in an extensive prodrug review
that was published in 2018.
1:17
This is a simplified
prodrug concept.
A drug promoiety
molecule is a prodrug.
According to the definition,
it is pharmacologically
inactive or
significantly less active
than the parent drug.
The barrier which a
prodrug should overcome
can be basically any
biological barrier,
such as an epithelial barrier,
or it can be a
physicochemical barrier,
such as poor solubility
or poor lipophilicity.
Both can result in poor
absorption and so on.
Once the prodrug has
overcome the barrier as an
inactive compound, it
must undergo conversion,
which, in most cases, is
an enzymatic conversion
to release the active
parent drug in the body.
