for natural logarithms:
lnCp¼lnC 0 kelt (8:6)
and for logarithms to base 10:
log 10 Cp¼log 10 C 0
kelt
2 : 303
(8:7)
Both these equations give straight line plots (Figure 8.6) and so it is possible
to obtain a value ofkelby measuring the slope of the graph provided the
experimental data gives a reasonable straight line. Thet1/2value may also be
calculated from these graphs. However, it is advisable to take an average of
several measurements oft1/2made from different initial values ofCpin order to
obtain an accuratet1/2value.
Log 10 Co−kel2.303
−log 102
t1/2Time t Time tLog 10 Cp Log 10 Cp
Log 10 CpLog 10 (Cp/2)Slope ==t1/2Figure 8.6 Determination of the values oft1/2andkelfrom logarithmic plots of plasma concen-
tration against time. The logarithm plot for logs to base ten is shown but the natural logarithmic
plot would be similar except the slope would now be equal tokelHalf-life andkelvalues may be used to put the comparison of the pharmaco-
logical effect of a lead with its analogues on a numerical basis. This could provide
an indication of the best course of action to take for the successful development of
a useful drug. For example, if a lead has a short duration of action, analogues
with largert1/2and smallerkelvalues than those of the lead are more likely to give
the required pharmacological effect. Similarly, if the lead is too toxic, analogues
with smallert1/2and largerkelvalues need to be developed. It is emphasized that
t1/2andkeldata are not infallible and should not be considered in isolation.
8.4.2 Clearance and its significance
Clearance (CL) is defined as thevolumeof blood in a specified region of the body
that is cleared of a drug inunit time. It is the parameter that relates the rate of
166 PHARMACOKINETICS