Cp}PlateauCpvalues
x x xxx xx
TimetFigure 8.11 The general changes in plasma concentration with time for repeated oral doses.
Repeat doses were administered at regular times intervalsx
obtain the desired therapeutic effect. This can only be achieved by the use of
repeat doses at regular time intervals. Initially, for each dose, the rate of absorp-
tion will exceed the rate of elimination and so the plasma concentration of the
drug will steadily increase as the number of doses increases (Figure 8.11). How-
ever, as the plasma concentration increases so does the rate of elimination and so,
eventually, the plasma concentration will reach a plateau. The value of the plateau
plasma concentration will vary between a maximum and minimum value, the time
interval between these values depending on the time interval between the doses.
The values ofkabandkelmay be used to calculate the plateau maximum and
minimum drug plasma concentration values. This is useful in designing multiple
dosage form regimens.
The time taken to achieve a plateau concentration may be reduced by using a
larger than usual initial dose. Thisloading dose, as it is known, gives a relatively
high initial plasma concentration, which acts as an elevated starting point for
the succeeding normal doses. This reduces the time taken to reach the plateau
concentration, that is, the therapeutic window, and so can be particularly useful
in cases of serious illness.
8.6 The use of pharmacokinetics in drug design
Pharmacokinetic data is used to differentiate between active substances with
good and poor pharmacokinetic characteristics. For example, substances
with poor absorption, high first pass metabolism and an unsuitable half-life
(too long or too short) will normally be discarded in favour of substances with
more appropriate pharmacokinetic properties.
Pharmacokinetics is used in all the development stages of a drug from
preclinical to Phase IV trials (see section 11.3). Legislation normally demands
THE USE OF PHARMACOKINETICS IN DRUG DESIGN 177