Abstracts

Rationale: Phenytoin (PHT) is the most commonly prescribed antiepileptic drug in the elderly. Little is known about its pharmacokinetics (PK) in this age group. We characterized PHT PK in elderly and younger patients using a stable-labeled PHT isotope. Methods: Patients on steady-state maintenance PHT therapy were given a single intravenous 100 mg injection of [2-13C,1,3-15N2] 5,5-diphenylhydantoin as part of their daily regimen. Patients taking potentially interacting co-medications were excluded. Blood samples were collected just prior to and up to 192 hours after the isotope dose. Both labeled and unlabeled PHT were measured using a gas chromatographic-mass spectrometric assay. Unbound drug was separated from total PHT by ultrafiltration. PK analysis was done with WINNONLIN 3.0 using a non-compartmental approach. Results: Ten elderly and six younger adults have been studied to date. Mean age for the two groups were 73.7?7.1 and 32?8.6 years, respectively. The PK values (mean?SD) are reported in the table. No statistical differences were seen in the PK values between the two age groups. Conclusions: These results indicate that steady-state PHT PK varies widely among patients. Elimination half-lives in the majority of young and elderly subjects are greater than 24 hours regardless of serum PHT concentration which may allow once a day dosing. In this interim analysis, the wide variability and small sample size preclude meaningful comparison between the two age groups. Supported by NIH-NINDS P50-NS16308 and M01-RR00400.