A comparison between microcrystalline and conventional phenytoin preparations: relative bioavailability and steady-state plasma concentrations

Plasma concentrations of two phenytoin products (a conventional phenytoin acid preparation and a microcrystalline form of phenytoin acid) were studied after single dose administration and during steady-state conditions in four healthy male volunteers. Relative bioavailability for the conventional tablet in comparison with the microcrystallin was in the range of 48-80% during single dose administration and in the range 54-95% at steady-rate. The microcrystalline preparation gave, as expected, a higher rate of absorption. During steady-state conditions, however, this higher rate of absorption was associated with considerable fluctuations in plamsa concentration during the dosage interval. The mean maximum plasma concentration was about 50% high than the value at the beginning of the dose interval (2-dose concentration value) when the microcrystalline product was administered. The corresponding figure was only about 25% for the conventional tablet. Since upward fluctuations in plasma concentrations may be associated with side effects, the more even level obtained with the conventional product may be an advantage from the clinical point of view. An incresed rate of bioavailability is not a clinical improvement if it occurs at the expense of greater fluctuations in plasma concentration during the dose interval.