The effect of a high-fat meal on the absorption of 100-mg Dilantin Kapseals and 100-mg Mylan extended-release phenytoin sodium capsules was determined in a single-dose, two-way crossover study conducted at the University of Florida, Gainesville, FL. Bioavailability of Mylan administered with food was 13% lower than that of Dilantin Kapseals, an effect resulting in a median 37% decrease in plasma phenytoin and subtherapeutic levels in 46% of patients. Simulations of substituting Dilantin for Mylan result in a 15% increase in bioavailability, a median 102% increase in plasma phenytoin and toxic levels in 84% of patients. Food effect studies of bioavailability are important in FDA regulations regarding bioequivalence of phenytoin products. [1]

COMMENT. When administering phenytoin products with meals, the observed alterations in bioavailability may cause significant changes in therapeutic efficacy or toxicity. The substitution of Mylan, an extended phenytoin capsule, for Dilantin Kapseals can result in decreased phenytoin serum levels and impaired seizure control. The authors recommendations to prevent unintended alterations in PHT concentrations when switching products include the following: If a change to Mylan is considered necessary, take 1 hour before meals, not with meals, and monitor levels closely, especially with higher dose and blood levels.

Effect of food on bioavailability of Dilantin Kapseals. Dr Wilder and colleagues at the University of Florida have also examined the effect of food on a single 100 mg dose of Dilantin Kapseals, given 1) after an 8-hour fast and 2) after a high-fat meal, in a nonblinded, randomized, crossover trial [2]. In 24 healthy adult volunteers, absorption of Dilantin was not significantly different under fasting and fed conditions. It is suggested that Dilantin Kapseals may be administered without regard to meal times, at least in healthy adults.