Okay. So, in the previous lectures, we looked
at receptors and also enzymes. And now, what
I would like to do is consider the journey
that a drug makes; breaking down the different
parts of the journey of a drug into the different
phases: the pharmaceutical phase, the pharmacokinetic
phase and also, the pharmacodynamic phase.
In the pharmaceutical phase, a drug is disintegrated
from its dosage form by dissolution of the
active substrate. Pharmacokinetically, it
is then either absorbed, then distributed,
metabolised and excreted. The pharmacodynamic
phase pertains directly to the efficacy of
the drug receptor interaction, specifically
in the target tissue.
When we consider the purpose of the pharmaceutical
phase, this is to optimise the pharmaceutical
availability, making sure that there is drug
available for absorption in the first place.
Within the pharmacokinetic phase, optimisation
of biological availability i.e. for example,
a drug’s availability to be absorbed and
also, to travel to the right tissue where
it is supposed to function.
And finally, the pharmacodynamic phase, the
objective, of course, to optimise the required
biological effect which is the induction of
therapeutic effect. In other words, time to
reduce the amount of material we are actually
need to achieve a desired effect without
causing damage to surrounding tissues or interfering
with other receptors.
The pharmacokinetic phase for the drug to
be useful. The compound with the best binding
affinity for a target is not necessarily the
best drug. And indeed, it may actually show
poor activity in vivo. There are many instances
of this. For a drug to be useful, it must
first reach the target site. It must be absorbed
in sufficient quantity, distributed correctly
into the target tissue and should not be metabolised
too quickly or extensively, for example, via
first-pass metabolism in the liver.
We need to design drugs that can satisfy the
above. And so, therefore, having something
that works in vitro and actually interferes
directly with an enzyme is of no use from
a drug perspective unless it can actually
reach the target within an organism.
In terms of absorption, which is the first
instance of pharmacokinetic journey, most
drugs are given via the oral route. And why
is that? If a drug is typically given via
a non-intravenous route, not all of it may be
absorbed into circulation. Poor oral absorption
of the active drug can lead to poor bioavailability.
And this can be due to a number of factors:
drug lipophilicity, solubility, ionisation,
degradation, metabolism and physiology.
In general, the higher the lipophilicity of