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0:00
This is a talk for
the Henry Stewart Collection.
I'm Marc Pfister, a
trained nephrologist.
I worked in Switzerland and in
the US, in California at UCSF,
before I joined a couple of
pharmaceutical companies.
And now I work as
Chief Medical Officer
for a global consulting company.
The topic of this lecture is
"Pharmacometric Approaches
to Optimize Use of Drugs
and Dialysis Treatments
in Patients with
Chronic Kidney Disease."
0:36
Before we go to a
couple of case studies,
I want to briefly review the
concept of therapeutic window.
The goal of every
treatment in our patients
is to improve, extend, save lives.
So the goal is to optimize the
dosing so that patients have
maximum benefit and minimal risk
for adverse events, safety events.
To obtain that goal, we need to
understand the exposure range,
the concentration range for
a given drug and treatment.
And the goal is to have a maturity
of patients with this exposure
range so that, again, we can
optimize benefits and minimize
the risk for adverse
events for these patients.
And that range of
target concentrations
is called therapeutic window.
1:33
This is an example from
the cardiovascular space.
This plot shows a blue
line and a red line.
It compares a new class of drugs
to prevent thromboembolic events,
Factor Xa inhibitors, and compares
this new class with a standard
of care, which is
Enoxaparin, which is
shown as a black horizontal line.
The goal is to optimize dosing
for this new class of drug
so that the blue and the red
line are below the black line.
The blue line represents
thromboembolic events.
So the lower the number, the better.
That means more thromboembolic
events were protected.
The red line is
increasing with dose.
That is, the safety curve.
The higher dose, the
more bleeding events.
The same goal here is to have
this red line at the low level.
We can see that there is a window
in the middle where both the blue
and the red line are
below the black line.
So that means for
this class of drug,
there is a dose range that is
associated with better efficacy.
The blue line is
below the black line.
And also, better safety.
And that is the therapeutic
window for this class of drug.
And this plot is based on data
from a hundred different trials.
So the goal is with
pharmacometric approaches
to integrate data
from different trials
and to quantify this therapeutic
window so that we can compare
different compounds
and different doses
and optimize treatment for patients.
