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There are several advantages
in using these relative potency designs that directly compare
a range of doses of two preparations. (Beaver
et al., 1968; Laska
et al., 1984). First, the resulting relative potency
estimates allow clinicians to estimate the dose of a new
drug in the individual patient based on the previous dose
of the standard analgesic usually used by that patient.
Additionally, if one quantitates specific side effects along
with each pain measurement, relative potency studies allow
one to test whether a new analgesic or drug combination
is less toxic than the standard (Figure
6.3.1); the relative intensity of adverse effects can
be estimated for the two treatments at doses providing the
same analgesia.
There are also
pitfalls in interpreting single-dose relative potency assays.
The approach assumes that the effect ranges studied in the
two dose-response curves overlap, and that they are linear
and parallel, as in panel A. If the dose-response curves
are not parallel (C) or linearl (D) or if the doses chosen
are not in the same analgesic range (B)Æ
the calculated relative potency (denoted by Æ
in the figure) is meaningless (Figure 6.3.2).
In addition, if
the drugs to be compared have different kinetics, the relative
potency may vary greatly depending upon whether the peak
pain relief or the summed scores over time are used. For
example, using summed scores over time will favor a drug
with longer duration
(Figure
6.3.3).
Click
on image to enlarge
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Figure
6.3.3a
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Figure
6.3.3b
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| Four-point
relative potency study comparing intramuscular
(filled circles) and oral (open circles) phenazocine.
(a) Pain intensity difference (category scale)
is plotted against time (left). Note the difference
between the time course of analgesia for the two
routes. (b) total (left) or peak (right) change
in pain intensity are plotted against dose. For
total scores, oral phenazocine is one-fourth as
potent as seen with the two routes. Because the
time-course of response differs between the routes,
note that the relative potency calculated for
total scores will change according to the length
of the study; e.g. if only the first three hours
were considered, the infranuscular/oral disparity
would have appeared even greater. Beaver
et al., (1968) with permission. |
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