Drug Administration part VII

From Application to Distribution
in the Body
As a rule, drugs reach their target organs
via the blood. Therefore, they must first
enter the blood, usually the venous limb
of the circulation. There are several possible
sites of entry.
The drug may be injected or infused
intravenously, in which case the drug is
introduced directly into the bloodstream.
In subcutaneous or intramuscular
injection, the drug has to diffuse
from its site of application into the
blood. Because these procedures entail
injury to the outer skin, strict requirements
must be met concerning technique.
For that reason, the oral route
(i.e., simple application by mouth) involving
subsequent uptake of drug
across the gastrointestinal mucosa into
the blood is chosen much more frequently.
The disadvantage of this route
is that the drug must pass through the
liver on its way into the general circulation.
This fact assumes practical significance
with any drug that may be rapidly
transformed or possibly inactivated in
the liver (first-pass hepatic elimination;).
Even with rectal administration,
at least a fraction of the drug enters the
general circulation via the portal vein,
because only veins draining the short
terminal segment of the rectum communicate
directly with the inferior vena
cava. Hepatic passage is circumvented
when absorption occurs buccally or
sublingually, because venous blood
from the oral cavity drains directly into
the superior vena cava. The same would
apply to administration by inhalation
. However, with this route, a local
effect is usually intended; a systemic action
is intended only in exceptional cases.
Under certain conditions, drug can
also be applied percutaneously in the
form of a transdermal delivery system
. In this case, drug is slowly released
from the reservoir, and then penetrates
the epidermis and subepidermal
connective tissue where it enters blood
capillaries. Only a very few drugs can be
applied transdermally. The feasibility of
this route is determined by both the
physicochemical properties of the drug
and the therapeutic requirements
(acute vs. long-term effect).
Speed of absorption is determined
by the route and method of application.
It is fastest with intravenous injection,
less fast which intramuscular injection,
and slowest with subcutaneous injection.
When the drug is applied to the
oral mucosa (buccal, sublingual route),
plasma levels rise faster than with conventional
oral administration because
the drug preparation is deposited at its
actual site of absorption and very high
concentrations in saliva occur upon the
dissolution of a single dose. Thus, uptake
across the oral epithelium is accelerated.
The same does not hold true for
poorly water-soluble or poorly absorbable
drugs. Such agents should be given
orally, because both the volume of fluid
for dissolution and the absorbing surface
are much larger in the small intestine
than in the oral cavity.
Bioavailability is defined as the
fraction of a given drug dose that reaches
the circulation in unchanged form
and becomes available for systemic distribution.
The larger the presystemic
elimination, the smaller is the bioavailability
of an orally administered drug.