A comparative study of the bioavailability of five different phenytoin preparations

Abstract

The concentration of phenytoin in saliva has been measured in 8 healthy volunteers at intervals after an intravenous dose and after single oral doses of five formulations commercially available in the United Kingdom. The six doses (all 300 mg) were given in random order and at least one week apart. There were no significant differences in the mean values of the peak saliva concentration, the time-to-peak and the area under the saliva concentration-time curve between the five oral formulations. The absolute bioavailability of phenytoin varied between 68 and 74%.

Are there potential problems with generic substitution of antiepileptic drugs?

“…31 More recent studies on bioequivalence have reported differences in pharmacokinetic parameters between generic phenytoin and the innovator brand, 30,66,67 though some of these differences were small and considered unlikely to have clinical consequences. 29,68 Differences in the content of phenytoin between capsules of generic and branded preparations, rather than differences in the pharmacokinetics per se, have also been reported. 31 Differences in pharmacokinetic parameters between branded and generic formulations have been reported in Chinese subjects 69 and when taken with food, 16 which could have clinical implications.…”

“…P. Crawford et al This potential for differences in therapeutic response to AEDs, even though products are defined as bioequivalent, is a recurring theme in the literature, 1,2,5,6,19,23,24,[26][27][28][29][30][31] with a number of issues highlighted.…”