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Hello, I'm Jill Kolesar
and today's lecture
is the Overview of Clinical Pharmacology
Today, we will cover
some background information,
focus on pharmacokinetics,
and finalize it up with a summary.
What I'd like to talk to you about now
is an overview of drug development.
When a new chemical entity
first a great deal of pre-clinical
research is required to be done.
There is synthesis
and purification of the compound
and that's followed by animal testing,
both short-term and long-term
animal testing for toxicology.
There are also a number of
clinical pharmacology studies
that are performed at that time.
So probably, the most important one
is to get an idea of the metabolism,
so the drug is incubated
or using other model systems
to determine if it's metabolized
by a particular cytochrome P450 enzyme
or if it induces or inhibits
those enzymes as well.
The IC50 is determined
and so pharmacology really does play
a fairly large role
in the early testing of a new drug.
After all the testing
has been completed,
the next thing that happens is an IND
or Investigational New Drug application
is submitted to the FDA.
At that time, the FDA can determine
whether the drug is going to go on
to clinical testing or not,
and if it is going on
to clinical testing,
the initial phase clinical testing
is going to be phase I.
The goal of a phase I study is
to determine the maximum tolerated dose
and to really come up with a dose
that's going to be recommended
in phase II.
Phase I studies
are typically conducted in patients
that have advanced refractory cancers,
and they don't always have
a therapeutic endpoint,
although some patients do benefit.
The drug then goes on to phase II
if there's a small efficacy signal
and phase II will typically be in
a specific population
of only one disease type.
What we're seeing even more commonly now
is phase IIs
are actually conducted in patients
with a particular type of mutation.
So we're seeing
targeted therapies being approved
based on just phase II data.
though that are not as targeted
do go on to phase III studies,
and in the phase III study,
the new therapy
is compared to standard of care.
Clinical pharmacology does play a role
in all phases of this testing.
In between phase I and phase II,
there are usually food effect studies
if a drug can be administered
with or without food,
that doesn't form the package labeling.
There are also studies
that are conducted
in special populations,
which we'll talk
a little bit about more.
These special population studies
are for patients
who have renal and hepatic dysfunction
and to determine what the dose would be
in those special populations.
There are also a number of drug
that are conducted in the phase II
stage of drug development,
and we'll talk about all of these
and their study designs
in a little bit more detail
as the talk goes on.
Once clinical testing is completed,
the next thing that happens is an NDA
or New Drug Application
is submitted to the FDA.
At that point,
the FDA just makes a decision
whether the drug can be approved or not.
And they can approve it with no changes,
they can send it back
for additional studies
or they can just approve it.