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VOL. 70 (3), 663-679, 2004 PHARMACOKINETICS AND INDIVIDUALIZED DRUG THERAPY

In a study we recently have performed in Uppsala it was shown
that in 39 new patients treated with phenytoin only about 5% got a
prescribed dose that gave therapeutic plasma concentrations, while
about 47% either got too high or too low plasma concentrations. With
a Bayesian individualization program for phenytoin dosing it was fur-
thermore shown that it was possible to predict the correct dose in 95%
of patients treated with phenytoin. These examples demonstrate the
difficulties of individualization drug dosing without performing co-
rrect interpretations of measured plasma concentration values.

As mentioned before, for immunosuppressant drugs it is very
important to keep the drug concentrations within certain limits. If
you get too high concentrations you can have toxic effect of the drug
and the transplanted organ will be affected and if you get too low
concentration the body may reject the organ. In order to avoid this,
a number of blood samples are usually taken repeatedly in each
patient, almost every day, during the first weeks after the surgery. In
figure 10 is shown a patient that had much lower plasma concentra-
tions than expected in his population and if he had behaved as
expected, this patient should have had a plasma concentration-time
curve like the upper one, but instead he had low plasma concentra-
tion values as shown in the figure.

FIGURE 10. Kidney-transplanted patient treated with the immunosuppressant drug
sirolimus. Several drug analyses and dose adjustments performed. The upper curve
shows the blood concentration-time profile if this patient had behaved kinetically

as expected in his population.

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