Pharmacokinetics IV

Drug entry into hepatic and renal
tissue constitutes movement into the
organs of elimination. The characteristic
phasic time course of drug concentration
in plasma represents the sum of
the constituent processes of absorption,
distribution, and elimination,
which overlap in time. When distribution
takes place significantly faster than
elimination, there is an initial rapid and
then a greatly retarded fall in the plasma
level, the former being designated
the !-phase (distribution phase), the
latter the "-phase (elimination phase).
When the drug is distributed faster than
it is absorbed, the time course of the
plasma level can be described in mathematically
simplified form by the Bateman
function (k1 and k2 represent the
rate constants for absorption and elimination,
respectively).
B. The velocity of absorption depends
on the route of administration.
The more rapid the administration, the
shorter will be the time (tmax) required
to reach the peak plasma level (cmax),
the higher will be the cmax, and the earlier
the plasma level will begin to fall
again.
The area under the plasma level time
curve (AUC) is independent of the route
of administration, provided the doses
and bioavailability are the same (Dost’s
law of corresponding areas). The AUC
can thus be used to determine the bioavailability
F of a drug. The ratio of AUC
values determined after oral or intravenous
administration of a given dose of a
particular drug corresponds to the proportion
of drug entering the systemic
circulation after oral administration.
The determination of plasma levels affords
a comparison of different proprietary
preparations containing the same
drug in the same dosage. Identical plasma
level time-curves of different
manufacturers’ products with reference
to a standard preparation indicate bioequivalence
of the preparation under
investigation with the standard.