Absence of Food Effect on the Extent of Alprazolam Absorption from an Orally Disintegrating Tablet

Study Objective. To evaluate the effect of a standardized meal on the bioavailability of alprazolam formulated as an immediate‐release orally disintegrating tablet (ODT) in healthy volunteers. Design. Single‐dose, randomized, open‐label, two‐period crossover study. Setting. Contract research organization clinic. Subjects. Sixteen healthy volunteers (seven men, nine women), aged 20–50 years. Intervention. Subjects were administered a single dose of alprazolam ODT 1.0 mg during two treatment periods—under fasting conditions and after a standard high‐fat breakfast—separated by a 7‐day washout period. Measurements and Main Results. Blood samples for determination of alprazolam pharmacokinetics were collected by venipuncture up to 72 hours after dosing. A validated liquid chromatography with tandem mass spectrometry detection method was used to quantify the alprazolam plasma concentration. The overall extent of alprazolam absorption from the ODT formulation, as measured by area under the concentration‐time curve, was unaffected during fed conditions. However, the rate of alprazolam absorption was slower after administration during fed relative to fasted conditions. The mean maximum observed plasma concentration (Cmax) decreased approximately 25%, and time to Cmax (Tmax) was delayed approximately 1.5 hours when food was administered before dosing. Conclusion. Coadministration of food was shown to have no effect on extent of absorption of immediate‐release alprazolam ODT 1.0 mg when compared with drug administration in the fasted condition; however, the rate of drug absorption was decreased. The clinical significance of the difference in rate of alprazolam absorption is unknown but thought to be minimal.