Bioavailability of phenytoin on single and multiple oral doses of two dosage forms in normal subjects

The extent and rate of absorption of phenytoin (PHT) from tablet and powder were studied in four healthy adult volunteers. It was demonstrated by urinary and fecal excretion that the almost all quantity of PHT in tablet was absorbed through the gastrointestinal tract, and the observed values of the estimated free concentration (Cest.f) estimated from mixed saliva concentration of PHT in the multiple dose were in fair agreement with the calculated values of that by using computer simulation in case of tablet. On the contrary, the variations were observed in Cest.f using therapeutic dose of PHT powder. The values of Cest.f at steady-state in tablet administration were higher than those in powder administration. The absorption ratio of PHT powder was low and variable, and decreased upon increase of dose. The ratio calculated from the Cest.f values of both dosage forms at steady-state were in good correspondence to the observed values of PHT excreted in feces.