Changes in Serum Phenytoin Concentrations in Epileptic Patients Produced by Changing Phenytoin Preparation from Granular Form to a Novel 10% Powder.

Abstract

Purpose: It is well known that there is a significant difference in the bioavailability of different preparations of phenytoin (PHT). A novel 10 % powder formulation of PHT (Aleviatino‐10 % powder), which was believed to have equivalent bioavailability to the tablet and granular formulations, was developed by Dainippon Pharmaceutical Co., LTD. in 1997. This lead us to switch 12 outpatients with epilepsy from the granular preparation of PHT (Aleviatino‐granules) to the novel 10 96 powder. Here, we report that changing the PHT formulation from the granular to the novel powder form produced a significant change in hioavailability. Methods: Subjects consisted of 8 men and 4 women with epilepsy; mean age, 32.7 years; range, 21–58 years; 2 generalized epilepsies and 10 localization‐related epilepsies recruited from the outpatient clinics. The dose of the granular form of PHT was 90‐390 mg/day (mean, 258.3 mg/day). Four patients received only PHT and the remaining patients received PHT and at least 1 other AED. The serum PHT concentrations were determined prior to and more than 2 weeks after changing the formulations. We used the same dose for each preparation, and the dose of any other anticonvulsant drug taken by the patients was not changed during the study. Results: The mean serum PHT level was significantly elevated from 9.66 to 19.51 pg/ml after switching the patients to the 10% powder formulation (p < 0.01). The mean ratio of serum PHT concentrations (S, pg/ml) to dose (D, mgikgiday), i.e. S/D ratio, was also increased significantly from 2.1 to 4.3 after switching preparations (p < 0.01). A decrease in the dose (mean, 85 %) was required in 6 patients. There was a significant positive correlation between extent of the elevation of serum PHT concentration after switching to the 10 % powder and serum PHT concentration before the switch (r = 0.86, p c 0.0003). Furthermore, the elevation of serum PHT levels in the patients receiving only PHT was significantly greater than that in the patients receiving 1 or more other anticonvulsants (p < 0.05). Cuncbsion: These results suggest that the 10% powder formulation of PHT (Aleviatino‐10% powder) has a significantly greater bioavailability than the granular form (Aleviatino‐granules). Therefore, one must be vigilant when switching patients from one formulation of PHT to another, particularly in patients receiving only PHT. In addition, upon switching, one should consider adjusting the dose to decrease the likelihood of adverse effects and interactions between PHT and other anticonvulsants.