PHENYTOIN AUTOINDUCTION

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.