Pharmacokinetic parameters

The parameters that best describe the

behaviour of drugs in the body are volume of
distribution (V) and clearance (CL).

V = the apparent volume available for drug
disposition.
CL = the ability of the body to eliminate drugs.
Volume of distribution
volume into which a drug is distributed at
equilibrium. the volume that would contain
the drug if its concentration throughout the
body was the same as in plasma.

Clearance
the volume of plasma from which a drug must be
entirely eliminated within a set time in order to
account for its removal from the body.
The rate of drug elimination is normally
proportional to [C], therefore CL is usually
constant.
Several sites (e.g. liver, lung, kidney, plasma) may
be involved in the elimination of a single drug; CL
is the sum of these individual clearances.
Several kind of clearance
Renal clearance
can be directly measured. When CLR is greater
than 70% CL, drug accumulation may occur in
patients with renal insufficiency.
Hepatic clearance
dependent on blood flow (Q) and the
extraction ratio (ER)
Clearance by other routes
eliminated from the body by non-renal and
non-hepatic routes. Ex. esters anaesthetic drugs
Half-life
the time required for [C] to decrease by 50%
during the terminal phase of decline.

k = constant (log 2 = 0.693)
steady-state concentrations are reached after
about 45 t12s.

Drugs are often given orally at intervals
that are about equal to their t12s; this
usually provides an acceptable
compromise between the decline in drug
concentrations after each dose, and the
maintenance of an acceptable [C].
Context-sensitive half-times (CSHT)
when drugs are given by intra-venous
infusion, computer-derived values for their
context-sensitive half-time (CSHT) are a better
indication of their disposition and activity than
t12s.
The CSHT can be defined as the time required
for the plasma concentration to decrease by
50% at the end of a specified period of
infusion.
For some drugs (e.g. remifentanil), the CSHT (35
minutes) is independent of the duration of infusion; its
effects are rapidly reversible, even after prolonged
infusions. In other instances (e.g. alfentanil,
midazolam, propofol) the CSHT is initially relatively
constant, but increases 23 times after infusions of 68
hours. By contrast, in these conditions the CSHT of
fentanyl increases 1012 times, and its effects may
persist for several hours after the termination of
prolonged infusions.
CSHTs are a useful indication of the disappearance of
drug activity after infusions of different durations, and
may therefore be of considerable value in total
intravenous anaesthesia.
AUC
area under the curve.
The area under the plasma level time curve
(AUC) is independent of the route of
administration, provided the doses and
bioavailability are the same (Dosts 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.