Drug Elimination X

Lipophilic drugs that are converted
in the liver to hydrophilic metabolites
permit better control, because the
lipophilic agent can be eliminated in
this manner. The speed of formation of
hydrophilic metabolite determines the
drug’s length of stay in the body.
If hepatic conversion to a polar metabolite
is rapid, only a portion of the
absorbed drug enters the systemic circulation
in unchanged form, the remainder
having undergone presystemic
(first-pass) elimination. When biotransformation
is rapid, oral administration
of the drug is impossible (e.g.,
glyceryl trinitate). Parenteral or,
alternatively, sublingual, intranasal, or
transdermal administration is then required
in order to bypass the liver. Irrespective
of the route of administration,
a portion of administered drug may be
taken up into and transiently stored in
lung tissue before entering the general
circulation. This also constitutes presystemic
elimination.
Presystemic elimination refers to
the fraction of drug absorbed that is
excluded from the general circulation
by biotransformation or by first-pass
binding.
Presystemic elimination diminishes
the bioavailability of a drug after its
oral administration. Absolute bioavailability
= systemically available amount/
dose administered; relative bioavailability
= availability of a drug contained
in a test preparation with reference to a
standard preparation.