ately start to fall because of elimination processes (Figure 8.4(a) ). However,
the plasma concentration of a drug administered by intravenous infusion will
increase with time until the rate of infusion is equal to the rate of elimination
(Figure 8.4(b) ). At this point the drug plasma concentration remains constant
until infusion is stopped whereupon it falls.
8.4.1 Intravenous injection (IV bolus)
The administration of a drug by a rapid intravenous injection places the drug in
the circulatory system where it is distributed (see section 2.7.1) to all the
accessible body compartments and tissues. The one compartment model (Figure
8.3(a) ) of drug distribution assumes that the administration and distribution of
the drug in the plasma and associated tissues is instantaneous. This does not
happen in practice and is one of the possible sources of error when using this
model to analyse experimental pharmacokinetic data.
(a) Time Time
Cp CpInfusion stopped(b)Figure 8.4 The variation of the concentration of a drug in the plasma (Cp) with time when
administered by (a) a rapid single intravenous injection and (b) intravenous infusion. With rapid
intravenous injections the graph does not show the time taken to carry out the injection; it is
normally taken as being spontaneous. In these cases the curve starts at the point where the first
plasma concentration measurements were taken
Once in the circulatory system the concentration of the drug begins to decline
(Figure 8.4(a) ). This decline, which is due to elimination processes (see section
2.7.1), is normally recorded by plotting a graph of the plasma concentration of
the drug against time. These graphs are usually close to being exponential curves
(Figure 8.4(a) ), that is, elimination normally exhibitsfirst order kinetics. This
observation enables medicinal chemists to describe these elimination processes
to an acceptable degree of accuracy by the mathematical equations used forfirst
order kinetics, that is:
rate of elimination¼kelC (8:1)
INTRAVASCULAR ADMINISTRATION 163