Information regarding phenytoin auto-induction is sparse and conflicti
ng. However. confirmation of the presence or absence of auto-induction
by phenytoin could have important implications in phenytoin therapy a
nd research. This was an open, randomized, three-way crossover study i
n which each of the eighteen volunteers received three different formu
lations of phenytoin, which was allocated in a random order. The perio
d effect between each crossover was determined to assess the effect of
the previous exposure to phenytoin on the area under the concentratio
n-time curve (AUC). The point estimate ratio of AUC(o-t) for the third
dose relative to the first dose was 81.19% with 90% t-confidence limi
ts of 74.37% to 88.00% and p = 0.3847. The point estimate ratio of AUC
(o-infinity) for the third dose relative to the first dose was 76.25%
with 90% t-confidence limits of 65.3% to 87.2% and p = 0.7169. These r
esults suggest that the AUC(o-infinity) and AUC(o-t) measured after th
e third dose of phenytoin was statistically significantly smaller than
those measured after the first dose. This decrease in AUC after the t
hird dose of phenytoin is probably caused by enhanced elimination of t
he drug as a result of enzyme induction.