Abstracts

RATIONALE: The objective of this study was to compare the relative bioavailability of Mylan extended phenytoin sodium capsules to Parke-Davis Dilantin[reg]Kapseals[reg] capsules under fasting conditions following a single, oral 100 mg (1 x 100 mg) dose in healthy, non-smoking, male subjects age 18-50.
METHODS: After a supervised overnight fast of at least 10 hours, each subject received either a single, oral 100 mg (1 x 100 mg) dose of Mylan extended phenytoin sodium capsules or Parke-Davis Dilantin[reg]Kapseals[reg] capsules with 240 mL of water. Water was not permitted for 2 hours before and until 2 hours after dosing, but was allowed at all other times. A three week washout separated each period. Serial blood samples (1 x 10 mL) were collected at predose and at 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 8.0, 12, 16, 24, 36, 48, 72 and 96 hours post-dose. Plasma samples were stored at -70[degree]C [plusminus] 15[degree]C until analysis. Samples were assayed at the Pharmacokinetics Laboratory of Mylan Pharmaceuticals Inc. The assay was linear from 0.05 [mu]g/mL to 10.0 [mu]g/mL. The method developed for the analysis of plasma phenytoin is performed using a High Performance Liquid Chromatography with ultraviolet detection which had a limit of quantification of 0.05 [mu]g/mL. The between-day precision of the assay was 6.1% or less. The between-day accuracy varied within -3.4% and 3.1% of the nominal concentration. Single-dose pharmacokinetic parameters for phenytoin were calculated using noncompartmental techniques. Statistical analyses were performed on the pharmacokinetic parameters using the General Linear Models Procedure (PROC GLM) of SAS Software (SAS Institute, Cary, NC).
RESULTS: Twenty-two subjects completed this study. Statistical analysis of the data reveals that 90% confidence intervals are 92% - 102%, 93% - 101% and 86% - 99% for the natural log transformed parameters LNAUCL, LNAUCI and LNCPEAK, respectively and they are within the acceptable bioequivalent range of 80% and 125%. In addition the 95% and 99% confidence intervals for the same parameters are within the 80-125% range as well.
CONCLUSIONS: This study demonstrates that Mylan[ssquote]s 100 mg extended phenytoin sodium capsules are bioequivalent to Parke-Davis Dilantin[reg]Kapseals[reg] 100 mg capsules following a single, oral 100 mg (1 x 100 mg) dose under fasting conditions.
Support: Mylan Pharmaceuticals Inc.
Disclosure: Salary - All the authors are Mylan Pharmaceuticals Inc. employees. Stock - All the authors have stock options from Mylan Pharmaceuticals Inc.