Effect of food on absorption of Dilantin Kapseals and Mylan extended phenytoin sodium capsules

Background: Because of phenytoin's narrow therapeutic index and nonlinear p harmacokinetics, food-induced alterations in absorption may markedly influe nce drug concentrations and, in turn, safety and effectiveness. Potential f ood-associated differences between 100-mg Mylan (Mylan Pharmaceuticals) ext ended-release phenytoin sodium capsules and Parke-Davis 100-mg Dilantin Kap seals were examined. Methods: A single-dose, two-way crossover study was co nducted in 24 healthy subjects to determine the effect of a high-fat meal o n the pharmacokinetics of both formulations. Pharmacokinetic parameters wer e estimated by noncompartmental methods. The impact of switching products o n steady-state phenytoin concentrations was investigated through simulation using pharmacokinetic data previously obtained from 30 epileptic patients. Results: Based on AUC(0-infinity), bioavailability of the Mylan product ad ministered with food was 13% lower than that observed with Dilantin Kapseal s. Simulations of substituting the Mylan product for Dilantin suggested tha t the 13% decrease in bioavailability would result in a median 37%, decreas e (range 19 to 58%) in plasma phenytoin concentrations when the drug is giv en with food; in 46%, of patients, phenytoin concentrations would likely fa ll below the therapeutic range of 10 to 20 mg/L. Simulations of substitutin g Dilantin for the Mylan product suggested that the 15% increase in bioavai lability would result in a median 102% increase (range 24 to > 150%) in pla sma phenytoin concentrations, with 84% of patients having phenytoin concent rations above the therapeutic range. Conclusions: Results suggest that when taking phenytoin sodium with food, product switches may result in either s ide effects or loss of seizure control.